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1
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Gottesman RF, Egle M, Groechel RC, Mughal A. Blood pressure and the brain: the conundrum of hypertension and dementia. Cardiovasc Res 2025; 120:2360-2372. [PMID: 40084805 DOI: 10.1093/cvr/cvaf010] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 11/04/2024] [Accepted: 12/09/2024] [Indexed: 03/16/2025] Open
Abstract
As the population ages, the anticipated rates of dementia worldwide are likely to increase dramatically, especially in low- and middle-income countries; thus, any opportunity to modify dementia risk is especially critical. Hypertension is one risk factor that is highly prevalent, consistently important for late-life brain health, and which could represent a target for prevention of dementia. Furthermore, hypertension is the most significant modifiable risk factor for stroke. This review will summarize existing literature linking hypertension with dementia and brain health more broadly, will discuss potential mechanisms linking hypertension with brain health, and will consider specific factors that may impact not only the relationship between hypertension and the brain but also the importance of treatment, including different associations over the life course.
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Affiliation(s)
- Rebecca F Gottesman
- Stroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, Building 10, 4D37, 10 Center Drive, Bethesda, MD 20814, USA
| | - Marco Egle
- Stroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, Building 10, 4D37, 10 Center Drive, Bethesda, MD 20814, USA
| | - Renee C Groechel
- Stroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, Building 10, 4D37, 10 Center Drive, Bethesda, MD 20814, USA
| | - Amreen Mughal
- Stroke Branch, National Institute of Neurological Disorders and Stroke Intramural Research Program, Building 10, 4D37, 10 Center Drive, Bethesda, MD 20814, USA
- Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute Intramural Research Program, Bethesda, MD 20814, USA
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2
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Casciaro M, Di Micco P, Tonacci A, Vatrano M, Russo V, Siniscalchi C, Gangemi S, Imbalzano E. Predictors of Acute Myocardial Infarction: A Machine Learning Analysis After a 7-Year Follow-Up. Clin Pract 2025; 15:72. [PMID: 40310307 PMCID: PMC12025629 DOI: 10.3390/clinpract15040072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Revised: 03/15/2025] [Accepted: 03/27/2025] [Indexed: 05/02/2025] Open
Abstract
Background: Ischemic heart disease is a major global health problem with significant morbidity and mortality. Several cardiometabolic variables play a key role in the incidence of adverse cardiovascular outcomes. Objectives: The aim of the present study was to apply a machine learning approach to investigate factors that can predict acute coronary syndrome in patients with a previous episode. Methods: We recruited 652 patients, admitted to the hospital for acute coronary syndrome, eligible if undergoing immediate coronary revascularization procedures for ST-segment-elevation myocardial infarction or coronary revascularization procedures within 24 h. Results: Baseline pulse wave velocity appears to be the most predictive variable overall, followed by the occurrence of left ventricular hypertrophy and left ventricular end-diastolic diameters. We found that the potential of machine learning to predict life-threatening events is significant. Conclusions: Machine learning algorithms can be used to create models to identify patients at risk for acute myocardial infarction. However, great care must be taken with data quality and ethical use of these algorithms.
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Affiliation(s)
- Marco Casciaro
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (M.C.); (S.G.)
| | - Pierpaolo Di Micco
- UOC Medicina Interna, AFO Medica, P.O. Santa Maria delle Grazie, ASL Napoli 2 Nord, 80076 Pozzuoli, Italy;
| | - Alessandro Tonacci
- Institute of Clinical Physiology, National Research Council of Italy (IFC-CNR), Via G. Moruzzi 1, 56124 Pisa, Italy;
| | - Marco Vatrano
- Cardiology Unit, “Pugliese-Ciaccio” Hospital, 88100 Catanzaro, Italy;
| | - Vincenzo Russo
- Cardiology Unit, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”-Monaldi Hospital, Piazzale Ettore Ruggeri, 80131 Naples, Italy;
| | - Carmine Siniscalchi
- Department of Continuity of Care and Multicomplexity, Azienda Ospedaliero-Universitaria di Parma, 43126 Parma, Italy
| | - Sebastiano Gangemi
- Allergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (M.C.); (S.G.)
| | - Egidio Imbalzano
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy;
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3
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Zhu C, Bishop T, Gregorich ZR, Guo W. Titin is a new factor regulating arterial stiffness through vascular smooth muscle cell tone in male rats. Physiol Rep 2025; 13:e70270. [PMID: 40119572 PMCID: PMC11928681 DOI: 10.14814/phy2.70270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 02/03/2025] [Accepted: 02/28/2025] [Indexed: 03/24/2025] Open
Abstract
Arterial stiffness is a robust predictor of cardiovascular disease and mortality. As such, there is substantial interest in uncovering its causal factors for the development of targeted treatments to regulate arterial stiffness. The elastic protein titin is a key determinant of myocardial stiffness, yet whether it plays a role in regulating arterial stiffness is unknown. In this study, we aimed to investigate the role of titin in vascular smooth muscle cell (VSMC) and overall arterial stiffness. To do this, we took advantage of rats lacking RNA binding motif 20 (RBM20), the primary splicing regulator of titin, in striated muscles. Using this model, we demonstrate that RBM20 regulates titin isoform expression in smooth muscle, with loss of the protein leading to the expression of larger titin isoforms. We show that the expression of larger titin reduces the stiffness of VSMCs. While decreased titin-based VSMC stiffness did not affect baseline arterial stiffness, we found that arterial stiffness was reduced in response to a challenge with the potent vasoconstrictor angiotensin II (Ang II). The observed reduction in arterial stiffness following Ang II treatment was not the result of changes in either the extracellular matrix or myofilaments. We further show that the expression of a larger titin isoform ameliorates cardiac remodeling caused by Ang II-associated hypertension. In summary, our study provides the first evidence that titin regulates VSMC stiffness, which is relevant for arterial stiffness in the context of elevated blood pressure. Furthermore, our data provide proof-of-concept evidence that targeting RBM20 to reduce arterial stiffness through titin isoform switching may benefit aging- or hypertension-associated arterial stiffness and vascular diseases.
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MESH Headings
- Animals
- Connectin/metabolism
- Connectin/genetics
- Vascular Stiffness/physiology
- Male
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/physiology
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/cytology
- Rats
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- Myocytes, Smooth Muscle/metabolism
- Myocytes, Smooth Muscle/physiology
- Rats, Sprague-Dawley
- Angiotensin II/pharmacology
- Protein Isoforms/metabolism
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Affiliation(s)
- Chaoqun Zhu
- Department of Animal SciencesUniversity of WyomingLaramieWyomingUSA
| | | | - Zachery R. Gregorich
- Department of Animal and Dairy SciencesUniversity of Wisconsin‐MadisonMadisonWisconsinUSA
- Cardiovascular Research CenterUniversity of Wisconsin‐MadisonMadisonWisconsinUSA
| | - Wei Guo
- Department of Animal SciencesUniversity of WyomingLaramieWyomingUSA
- Department of Animal and Dairy SciencesUniversity of Wisconsin‐MadisonMadisonWisconsinUSA
- Cardiovascular Research CenterUniversity of Wisconsin‐MadisonMadisonWisconsinUSA
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4
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Ibrahim AM, Roshdy M, Latif N, Elsawy A, Sarathchandra P, Hosny M, Hekal S, Attia A, Elmozy W, Elaithy A, Elguindy A, Afifi A, Aguib Y, Yacoub M. Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy. Circ Heart Fail 2025; 18:e012384. [PMID: 39846175 PMCID: PMC11832182 DOI: 10.1161/circheartfailure.124.012384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 11/14/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Changes in the phenotype and genotype in hypertrophic cardiomyopathy (HCM) are thought to involve the myocardium as well as extracardiac tissues. Here, we describe the structural and functional changes in the ascending aorta of obstructive patients with HCM. METHODS Changes in the aortic wall were studied in a cohort of 101 consecutive patients with HCM undergoing myectomy and 9 normal controls. Biopsies were examined histologically, immunohistochemically, and by electron microscopy. Changes in protein expression were quantified using morphometry and Western blotting. Pulse wave velocity was measured using cardiac magnetic resonance in 85 patients with HCM and compared with 117 age-matched normal controls. RESULTS In HCM, the number of medial lamellar units was significantly decreased, associated with an increase in interlamellar distance and aortic wall thickness, as compared with controls. Electron microscopy showed an altered lamellar structure with disorientation of elastin fibers from the circumferential direction. There was a significant decrease in collagen content, α-smooth muscle actin, smooth muscle myosin, smooth muscle 22 and integrin β1, as well as a significant increase in calponin and caspase-3. Fibulins 1, 2, and 5 showed reduced expression in HCM-aortic biopsies. Functionally, pulse wave velocity was significantly higher in patients with HCM compared with healthy controls, with an association between higher pulse wave velocity and more severe molecular and clinical parameters. CONCLUSIONS The increased wall stiffness observed in the aortas of obstructive patients with HCM is associated with structural alterations in the medial lamellar unit, including changes in smooth muscle cells and the extracellular matrix, indicating potential arterial dysfunction.
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Affiliation(s)
- Ayman M. Ibrahim
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
- Institute of Cardiovascular Physiology, University Göttingen, Germany (A.M.I.)
- Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt (A.M.I.)
| | - Mohamed Roshdy
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
| | - Najma Latif
- National Heart and Lung Institute, Imperial College London, United Kingdom (N.L., Y.A., M.Y.)
- The Magdi Yacoub Institute, Heart Science Centre, Harefield, United Kingdom (N.L., P.S.)
| | - Amr Elsawy
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
| | - Padmini Sarathchandra
- The Magdi Yacoub Institute, Heart Science Centre, Harefield, United Kingdom (N.L., P.S.)
| | - Mohammed Hosny
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
- Cardiology Department, Faculty of Medicine, Cairo University, Egypt (M.H.)
| | - Soha Hekal
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
| | - Ahmed Attia
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
- Institute of Cardiovascular Physiology, University Göttingen, Germany (A.M.I.)
- Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt (A.M.I.)
- National Heart and Lung Institute, Imperial College London, United Kingdom (N.L., Y.A., M.Y.)
- The Magdi Yacoub Institute, Heart Science Centre, Harefield, United Kingdom (N.L., P.S.)
- Cardiology Department, Faculty of Medicine, Cairo University, Egypt (M.H.)
| | - Wesam Elmozy
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
| | - Amany Elaithy
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
| | - Ahmed Elguindy
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
| | - Ahmed Afifi
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
| | - Yasmine Aguib
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
- National Heart and Lung Institute, Imperial College London, United Kingdom (N.L., Y.A., M.Y.)
| | - Magdi Yacoub
- Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.)
- National Heart and Lung Institute, Imperial College London, United Kingdom (N.L., Y.A., M.Y.)
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5
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Morrison BN, Mittermaier PM, Lester GR, Bodner ME, Cote AT. Sex differences in ventricular-vascular interactions associated with aerobic capacity. Echo Res Pract 2025; 12:2. [PMID: 39828701 PMCID: PMC11744966 DOI: 10.1186/s44156-024-00066-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 11/19/2024] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Aerobic capacity measured by maximal oxygen uptake (VO2max) is related to functional capacity and is a strong independent predictor of all-cause and disease-specific mortality. Sex-specific cardiac and vascular responses to endurance training have been observed, however, their relative contributions to VO2max are less understood. The purpose of this study was to evaluate sex-specific ventricular-vascular interactions associated with VO2max in healthy males and females. METHODS Sixty-eight males and females (38% females, 35 ± 10y) characterised as recreational exercisers to highly trained endurance athletes, and free of chronic disease underwent a cycle ergometer to assess VO2max. Resting arterial compliance and echocardiographic evaluation of left ventricular (LV) structure and function were measured and indexed to body surface area. RESULTS VO2max was similar between groups (54 ± 6 vs. 50 ± 7 ml/kg/min, p = 0.049). Indexed LV mass (LVMi) was higher (96 ± 15 vs. 81 ± 11, p = 0.001) in males versus females, respectively. Linear regression analysis revealed two models that were significantly associated with VO2max in males and females. In males, the two models included (1) longitudinal diastolic strain rate and LVMi (r2 = 0.31, p = 0.003) and (2) indexed end-diastolic volume (EDVi) and longitudinal diastolic strain rate (r2 = 0.34, p < 0.001). In females, the linear regression models included (1) LVMi, large arterial compliance, longitudinal systolic strain rate, and age (r2 = 0.69, p < 0.001) and (2) EDVi, large arterial compliance, longitudinal systolic strain rate, and age (r2 = 0.52, p = 0.003). CONCLUSION These findings reveal that while in both sexes, LVMi and LVEDVi are associated with VO2max, arterial compliance was also found to contribute to the variance in VO2 max in females, but not in males. Further, ventricular relaxation was a significant factor in aerobic capacity in males, while in females ventricular contraction was a significant factor.
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Affiliation(s)
- Barbara N Morrison
- School of Human Kinetics, Trinity Western University, CANIL Building, Rm. 115 22500 University Drive, Langley, BC, V2Y 1Y1, Canada
| | - Peter M Mittermaier
- Faculty of Natural & Applied Sciences, Trinity Western University, Langley, Canada
- Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Garth R Lester
- Faculty of Natural & Applied Sciences, Trinity Western University, Langley, Canada
- Faculty of Medicine, University of British Columbia, Vancouver, Canada
| | - Michael E Bodner
- School of Human Kinetics, Trinity Western University, CANIL Building, Rm. 115 22500 University Drive, Langley, BC, V2Y 1Y1, Canada
| | - Anita T Cote
- School of Human Kinetics, Trinity Western University, CANIL Building, Rm. 115 22500 University Drive, Langley, BC, V2Y 1Y1, Canada.
- Faculty of Medicine, University of British Columbia, Vancouver, Canada.
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6
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van der Linden IA, Roodenburg R, Nijhof SL, van der Ent CK, Venekamp RP, van der Laan SEI, Schipper HS. Early-Life Risk Factors for Carotid Intima-Media Thickness and Carotid Stiffness in Adolescence. JAMA Netw Open 2024; 7:e2434699. [PMID: 39302677 DOI: 10.1001/jamanetworkopen.2024.34699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/22/2024] Open
Abstract
Importance Atherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease later in life. Objective To identify early-life risk factors for preclinical atherosclerosis in adolescence. Design, Setting, and Participants This cohort study is part of the ongoing Wheezing Illness Study in Leidsche Rijn (WHISTLER) prospective birth cohort study, which includes 3005 healthy newborns born between December 2001 and December 2012 in the Leidsche Rijn area of Utrecht, the Netherlands. Eligible participants included those from the WHISTLER cohort who visited the clinic between March 2019 and October 2020 for adolescent follow-up. This study's analyses were performed in January 2024. Exposures Early-life growth was assessed at birth to 6 months, 5 years, and 12 to 16 years. Abdominal ultrasonography determined abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depth. Blood pressure (BP) percentiles and body mass index (BMI) z scores were used. Main Outcomes and Measures Carotid ultrasonography was performed at age 12 to 16 years to assess carotid intima-media thickness (cIMT) and the distensibility coefficient (DC), established measures of preclinical atherosclerosis. Multivariable linear regression models were used to identify early-life risk factors for cIMT and DC in adolescence. Results In total, 232 adolescents (median [IQR] age, 14.9 [13.7-15.8] years; 121 female [52.2%]) were included. More postnatal weight gain (B = 12.34; 95% CI, 2.39 to 22.39), higher systolic BP at 5 years (B = 0.52; 95% CI, 0.02 to 1.01), more VAT at 5 years (B = 3.48; 95% CI, 1.55 to 5.40), and a larger change in VAT between 5 and 12 to 16 years (B = 3.13; 95% CI, 1.87 to 4.39) were associated with a higher cIMT in adolescence. A higher BMI (B = -2.70, 95% CI,-4.59 to -0.80) and VAT at 5 years (B = -0.56; 95% CI, -0.87 to -0.25), as well as a larger change in BMI between 5 and 12 to 16 years (B = -3.63; 95% CI, -5.66 to -1.60) were associated with a higher carotid stiffness in adolescence. On the contrary, a larger change in SAT between 5 and 12 to 16 years (B = 0.37; 95% CI, 0.16 to 0.58) was associated with a higher carotid DC in adolescence. Conclusions and Relevance In this cohort study of 232 participants, early-life growth parameters, and particularly abdominal VAT development, were associated with a higher cIMT and carotid stiffness in adolescence. These findings suggest that assessment of adipose tissue development during childhood can aid characterization of lifetime risk trajectories and tailoring of cardiovascular prevention and risk management strategies.
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Affiliation(s)
- Isabelle A van der Linden
- Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Rozan Roodenburg
- Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Sanne L Nijhof
- Department of Social Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Cornelis K van der Ent
- Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Roderick P Venekamp
- Julius Center for Health Sciences and Primary Care, Department of General Practice & Nursing Science, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Sabine E I van der Laan
- Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Henk S Schipper
- Department of Pediatric Cardiology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, the Netherlands
- Department of Social Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
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7
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Nicolosi G, Donzella M, Polizzi A, Angjelova A, Santonocito S, Zanoli L, Annunziata M, Isola G. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients. Open Med (Wars) 2024; 19:20241003. [PMID: 39034949 PMCID: PMC11260002 DOI: 10.1515/med-2024-1003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 07/07/2024] [Accepted: 07/08/2024] [Indexed: 07/23/2024] Open
Abstract
OBJECTIVES This narrative review aims to update the current evidence and offer insight into the new non-invasive ultrasound techniques used to early identify degenerative vascular changes in subjects with periodontitis and to investigate if these methodologies could be useful to identify subclinical cardiovascular disease (CVD) dysfunction in periodontitis patients and to monitor changes in CVD risk after periodontal treatment. METHODS Studies examining the assessment of vascular endothelial function through the latest methodologies were analyzed. Systematic reviews, observational studies, and clinical trials in the English language were identified using PubMed, Web of Science, and Google Scholar databases with key search terms such as "periodontitis," "endothelial dysfunction (ED)," "arterial stiffness," and "periodontal therapy." RESULTS Several mechanisms are involved in the association between periodontitis and CVD. The key players are periodontal bacteria and their toxins, which can enter the circulation and infiltrate blood vessel walls. The increase in proinflammatory molecules such as interleukins and chemokines, c-reactive protein, fibrinogen, and oxidative stress also plays a decisive role. In addition, an increase in parameters of ED, arterial stiffness, and atherosclerosis, such as carotid intima-media thickness, pulse wave velocity, and flow-mediated dilatation, has been shown in periodontal patients. CONCLUSIONS The literature today agrees on the association of periodontitis and CVD and the positive role of periodontal therapy on systemic inflammatory indices and cardiovascular outcomes. Hopefully, these non-invasive methodologies could be extended to periodontal patients to provide a comprehensive understanding of the CVD-periodontitis link from the perspective of a personalized medicine approach in periodontology.
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Affiliation(s)
- Giada Nicolosi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124, Catania, Italy
| | - Martina Donzella
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124, Catania, Italy
| | - Alessandro Polizzi
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124, Catania, Italy
| | - Angela Angjelova
- University Dental Clinical Center St. Pantelejmon, Faculty of Dentistry, Ss. Cyril and Methodius University in Skopje, 1000, Skopje, North Macedonia
| | - Simona Santonocito
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124, Catania, Italy
| | - Luca Zanoli
- Department of Clinical and Experimental Medicine, University of Catania, 95123, Catania, Italy
| | - Marco Annunziata
- Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania Luigi Vanvitelli, 80138, Naples, Italy
| | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, 95124, Catania, Italy
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8
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Walser M, Arnold L, Mandilaras G, Funk C, Dalla-Pozza R, Pattathu J, Haas NA, Jakob A. Fontan Circulation and Aortic Stiffness: Insights into Vascular Dynamics and Haemodynamic Interplay. Pediatr Cardiol 2024:10.1007/s00246-024-03572-z. [PMID: 39008058 DOI: 10.1007/s00246-024-03572-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024]
Abstract
Increased aortic stiffness predisposes cardiac afterload and influences cardiac function. Congenital heart diseases involving aortic arch malformation and extended cardiovascular surgery, i.e. univentricular heart diseases, can lead to increased aortic stiffness. This study aimed to investigate whether Fontan patients (FO) have increased aortic stiffness within distinct aortic segments, and whether these parameters relate to Fontan-specific haemodynamics. In a prospective case-control study, 20 FO and 49 heart-transplanted control subjects with biventricular circulation underwent invasive cardiac catheterisation. We invasively measured pulse wave velocity (PWV) in the ascending aorta and along the entire aorta. Haemodynamic parameters, including end-diastolic pressure, pulmonary artery pressure, the cardiac index and systemic vascular resistance index were also assessed. FO exhibited significantly higher ascending aorta PWV (aPWV) than controls (FO: 7.2 ± 2.4 m/s|Controls: 4.9 ± 0.7 m/s, p < 0.001) and compared to the inner group central aorta PWV (cPWV; FO: 5.5 ± 1.2 m/s|Controls: 5.3 ± 1.0 m/s). Multivariate analysis confirmed this aPWV elevation in FO even after adjusting for age and BMI. aPWV and cPWV were almost identical within the control group. Correlation analyses revealed associations between cPWV and blood pressure in controls, while correlations were less apparent in FO. We detected no significant association between the aPWV and other haemodynamic parameters in any of our groups. FO exhibit increased aPWV, indicating specific vascular stiffness in the ascending aorta, while their overall aortic stiffness remains comparable to controls. Further research is needed to understand the implications of these findings on Fontan circulation and long-term cardiovascular health. CENTRAL MESSAGE Fontan patients show increased aortic arch pulse wave velocity, suggesting specific vascular stiffness. PERSPECTIVE STATEMENT Our study offers rare insights into pulse wave velocity in Fontan patients, highlighting increased arterial stiffness in the aortic arch. Vascular stiffness was particularly increased in the area of surgical reconstruction. This indicates the need for further research on vascular stiffness in Fontan circulation to understand its impact on cardiovascular health. CLINICAL TRIAL REGISTRATION German clinical trial registration, DRKS00015066.
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Affiliation(s)
- Matthias Walser
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Leonie Arnold
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Guido Mandilaras
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Christoph Funk
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Robert Dalla-Pozza
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Joseph Pattathu
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Nikolaus A Haas
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - André Jakob
- Department of Paediatric Cardiology and Paediatric Intensive Care, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany.
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9
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Yang H, Cull G, Yang M, Wang L, Fortune B, Gardiner SK. Differences in Systemic Pulse Waveform Between Individuals With Glaucoma, Glaucoma Suspects, and Healthy Controls. Invest Ophthalmol Vis Sci 2024; 65:20. [PMID: 38990070 PMCID: PMC11246099 DOI: 10.1167/iovs.65.8.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/12/2024] Open
Abstract
Purpose It has been hypothesized that compromised ocular circulation in glaucoma may be concomitant of systemic changes. The purpose of this study is to test whether systemic blood flow pulse waveform patterns differ between individuals with glaucoma (GL), glaucoma suspects (GLS), and normal healthy controls (HC). Methods The study included 35 bilateral GL, 67 bilateral GLS, 29 individuals with unilateral GL who were considered GLS in the other eye, and 44 healthy controls. Systemic pulsatile blood pressure waveforms were recorded using a finger cuff. A continuous 200 Hz plethysmography recording is made to obtain a pulse waveform. Waveform parameters were extracted using custom software from an average of eight pulse cycles. These were compared between GL, GLS, and HC groups on a per-eye basis, using generalized estimating equation models to account for intereye correlations; and plotted against disease severity by visual field linearized mean deviation (MDlin) and retinal nerve fiber layer thickness (RNFLT). Results Averaged blood pressure was significantly lower in the HC group (mean ± standard deviation 91.7 ±11.7 mm Hg) than the GLS (102.4 ± 13.9) or GL (102.8 ± 13.7) groups, with P < 0.0001 (generalized estimating equation regression). Waveform parameters representing vascular resistance were higher in both GLS and GL groups than the HC group; and were correlated with RNFLT and MDlin (P ≤ 0.05). Conclusions The shape of the systemic pulsatile waveform differs in individuals with GL/GLS suspects, compared to HC eyes. Blood pressure changes more rapidly in individuals with GL, which suggests higher arterial stiffness.
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Affiliation(s)
- Hongli Yang
- Discoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Health, Portland, Oregon, United States
| | - Grant Cull
- Discoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Health, Portland, Oregon, United States
| | - Mingrui Yang
- Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong Island
| | - Lin Wang
- Discoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Health, Portland, Oregon, United States
| | - Brad Fortune
- Discoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Health, Portland, Oregon, United States
| | - Stuart K Gardiner
- Discoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Health, Portland, Oregon, United States
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10
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Feitosa ADDM, Barroso WKS, Mion Junior D, Nobre F, Mota-Gomes MA, Jardim PCBV, Amodeo C, Oliveira AC, Alessi A, Sousa ALL, Brandão AA, Pio-Abreu A, Sposito AC, Pierin AMG, Paiva AMGD, Spinelli ACDS, Machado CA, Poli-de-Figueiredo CE, Rodrigues CIS, Forjaz CLDM, Sampaio DPS, Barbosa ECD, Freitas EVD, Cestario EDES, Muxfeldt ES, Lima Júnior E, Campana EMG, Feitosa FGAM, Consolim-Colombo FM, Almeida FAD, Silva GVD, Moreno Júnior H, Finimundi HC, Guimarães ICB, Gemelli JR, Barreto-Filho JAS, Vilela-Martin JF, Ribeiro JM, Yugar-Toledo JC, Magalhães LBNC, Drager LF, Bortolotto LA, Alves MADM, Malachias MVB, Neves MFT, Santos MC, Dinamarco N, Moreira Filho O, Passarelli Júnior O, Vitorino PVDO, Miranda RD, Bezerra R, Pedrosa RP, Paula RBD, Okawa RTP, Póvoa RMDS, Fuchs SC, Lima SGD, Inuzuka S, Ferreira-Filho SR, Fillho SHDP, Jardim TDSV, Guimarães Neto VDS, Koch VHK, Gusmão WDP, Oigman W, Nadruz Junior W. Brazilian Guidelines for In-office and Out-of-office Blood Pressure Measurement - 2023. Arq Bras Cardiol 2024; 121:e20240113. [PMID: 38695411 DOI: 10.36660/abc.20240113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/19/2024] Open
Affiliation(s)
- Audes Diogenes de Magalhães Feitosa
- Universidade Federal de Pernambuco (UFPE), Recife, PE - Brasil
- Pronto Socorro Cardiológico de Pernambuco (PROCAPE), Recife, PE - Brasil
- Instituto de Assistência, Pesquisa e Ensino em Saúde (IAPES), Recife, PE - Brasil
| | | | - Decio Mion Junior
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Fernando Nobre
- Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, SP - Brasil
| | - Marco Antonio Mota-Gomes
- Centro Universitário CESMAC, Maceió, AL - Brasil
- Hospital do Coração de Alagoas, Maceió, AL - Brasil
- Centro de Pesquisas Clínicas Dr. Marco Mota, Maceió, AL - Brasil
| | | | - Celso Amodeo
- Hcor, Associação Beneficente Síria, São Paulo, SP - Brasil
| | | | | | - Ana Luiza Lima Sousa
- Faculdade de Enfermagem da Universidade Federal de Goiás (UFG), Goiânia, GO - Brasil
| | | | - Andrea Pio-Abreu
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Andrei C Sposito
- Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo - Brasil
| | | | | | | | | | | | - Cibele Isaac Saad Rodrigues
- Pontifícia Universidade Católica de São Paulo, Faculdade de Ciências Médicas e da Saúde,Sorocaba, SP - Brasil
| | | | | | | | | | | | - Elizabeth Silaid Muxfeldt
- Universidade Federal do Rio de Janeiro (UFRJ), Hospital Universitário Clementino Fraga Filho - Programa de Hipertensão Arterial Resistente (ProHArt), Rio de Janeiro, RJ - Brasil
- Instituto de Educação Médica (IDOMED) - Universidade Estácio de Sá, Rio de Janeiro, RJ - Brasil
| | | | | | - Fabiana Gomes Aragão Magalhães Feitosa
- Universidade Federal de Pernambuco (UFPE), Recife, PE - Brasil
- Pronto Socorro Cardiológico de Pernambuco (PROCAPE), Recife, PE - Brasil
- Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, PE - Brasil
| | | | - Fernando Antônio de Almeida
- Pontifícia Universidade Católica de São Paulo, Faculdade de Ciências Médicas e da Saúde,Sorocaba, SP - Brasil
| | - Giovanio Vieira da Silva
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | | | | | | | | | | | | | - José Marcio Ribeiro
- Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte, MG - Brasil
- Hospital Felício Rocho, Belo Horizonte, MG - Brasil
| | | | | | - Luciano F Drager
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Luiz Aparecido Bortolotto
- Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo (Incor/FMUSP), São Paulo, SP - Brasil
| | | | - Marcus Vinícius Bolívar Malachias
- Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte, MG - Brasil
- Fundação Educacional Lucas Machado (FELUMA), Belo Horizonte, MG - Brasil
| | | | - Mayara Cedrim Santos
- Universidade Federal de Pernambuco (UFPE), Recife, PE - Brasil
- Instituto de Assistência, Pesquisa e Ensino em Saúde (IAPES), Recife, PE - Brasil
| | - Nelson Dinamarco
- Colegiado de Medicina - Universidade Estadual de Santa Cruz (UESC), Ilhéus, BA - Brasil
| | | | | | | | | | - Rodrigo Bezerra
- Pronto Socorro Cardiológico de Pernambuco (PROCAPE), Recife, PE - Brasil
- Laboratório de Imunopatologia Keizo Asami da Universidade Federal de Pernambuco, Recife, PE - Brasil
| | | | | | | | | | - Sandra C Fuchs
- Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS - Brasil
| | | | - Sayuri Inuzuka
- Unidade de Hipertensão Arterial - NIPEE - LHA/UFG, Goiânia, GO - Brasil
| | | | | | | | | | - Vera Hermina Kalika Koch
- Instituto da Criança e do adolescente do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP - Brasil
| | - Waléria Dantas Pereira Gusmão
- Centro Universitário CESMAC, Maceió, AL - Brasil
- Universidade Estadual de Ciências da Saúde de Alagoas (UNCISAL), Maceió, AL - Brasil
| | - Wille Oigman
- Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ - Brasil
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11
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Cheng L, Yue H, Zhang H, Liu Q, Du L, Liu X, Xie J, Shen Y. The influence of microenvironment stiffness on endothelial cell fate: Implication for occurrence and progression of atherosclerosis. Life Sci 2023; 334:122233. [PMID: 37918628 DOI: 10.1016/j.lfs.2023.122233] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/30/2023] [Accepted: 10/30/2023] [Indexed: 11/04/2023]
Abstract
Atherosclerosis, the primary cause of cardiovascular diseases (CVDs), is characterized by phenotypic changes in fibrous proliferation, chronic inflammation and lipid accumulation mediated by vascular endothelial cells (ECs) and vascular smooth muscle cells (SMCs) which are correlated with the stiffening and ectopic remodeling of local extracellular matrix (ECM). The native residents, ECs and SMCs, are not only affected by various chemical factors including inflammatory mediators and chemokines, but also by a range of physical stimuli, such as shear stress and ECM stiffness, presented in the microenvironmental niche. Especially, ECs, as a semi-selective barrier, can sense mechanical forces, respond quickly to changes in mechanical loading and provide context-specific adaptive responses to restore homeostasis. However, blood arteries undergo stiffening and lose their elasticity with age. Reports have shown that the ECM stiffening could influence EC fate by changing the cell adhesion, spreading, proliferation, cell to cell contact, migration and even communication with SMCs. The cell behaviour changes mediated by ECM stiffening are dependent on the activation of a signaling cascade of mechanoperception and mechanotransduction. Although the substantial evidence directly indicates the importance of ECM stiffening on the native ECs, the understanding about this complex interplay is still largely limited. In this review, we systematically summarize the roles of ECM stiffening on the behaviours of endothelial cells and elucidate the underlying details in biological mechanism, aiming to provide the process of how ECs integrate ECM mechanics and the highlights for bioaffinity of tissue-specific engineered scaffolds.
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Affiliation(s)
- Lin Cheng
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
| | - Hongyan Yue
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
| | - Huaiyi Zhang
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
| | - Qiao Liu
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
| | - Lingyu Du
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
| | - Xiaoheng Liu
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
| | - Jing Xie
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.
| | - Yang Shen
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China; JinFeng Laboratory, Chongqing 401329, China.
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12
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Badji A, Youwakim J, Cooper A, Westman E, Marseglia A. Vascular cognitive impairment - Past, present, and future challenges. Ageing Res Rev 2023; 90:102042. [PMID: 37634888 DOI: 10.1016/j.arr.2023.102042] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 08/29/2023]
Abstract
Vascular cognitive impairment (VCI) is a lifelong process encompassing a broad spectrum of cognitive disorders, ranging from subtle or mild deficits to prodromal and fully developed dementia, originating from cerebrovascular lesions such as large and small vessel disease. Genetic predisposition and environmental exposure to risk factors such as unhealthy lifestyles, hypertension, cardiovascular disease, and metabolic disorders will synergistically interact, yielding biochemical and structural brain changes, ultimately culminating in VCI. However, little is known about the pathological processes underlying VCI and the temporal dynamics between risk factors and disease mechanisms (biochemical and structural brain changes). This narrative review aims to provide an evidence-based summary of the link between individual vascular risk/disorders and cognitive dysfunction and the potential structural and biochemical pathophysiological processes. We also discuss some key challenges for future research on VCI. There is a need to shift from individual risk factors/disorders to comorbid vascular burden, identifying and integrating imaging and fluid biomarkers, implementing a life-course approach, considering possible neuroprotective influences of positive life exposures, and addressing biological sex at birth and gender differences. Finally, this review highlights the need for future researchers to leverage and integrate multidimensional data to advance our understanding of the mechanisms and pathophysiology of VCI.
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Affiliation(s)
- Atef Badji
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden
| | - Jessica Youwakim
- Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada; Centre interdisciplinaire de recherche sur le cerveau et l'apprentissage (CIRCA), Montreal, QC, Canada; Groupe de Recherche sur la Signalisation Neuronal et la Circuiterie (SNC), Montreal, QC, Canada
| | - Alexandra Cooper
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Eric Westman
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK
| | - Anna Marseglia
- Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
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13
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Jin L, Chen J, Wu L, Zhang M, Sun J, Shen C, Du L, Wang D, Li Z. Relative contributions of arterial stiffness to cardiovascular disease risk score in Chinese women in framingham and China-PAR model. Front Cardiovasc Med 2023; 10:1169250. [PMID: 37396573 PMCID: PMC10311511 DOI: 10.3389/fcvm.2023.1169250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 06/06/2023] [Indexed: 07/04/2023] Open
Abstract
Background Arterial stiffness played an important role in the development of cardiovascular disease (CVD) events. The aim of this study was to verify the relative importance of arterial stiffness for different CVD risk scores in a large sample of Chinese women. Methods We measured arterial velocity pulse index (AVI) and CVD risk scores in 2220 female participants (mean age 57 years). Framingham Risk Score (FRS), and the prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were used to estimate CVD risk, respectively. The relationships between AVI and risk scores were investigated by linear regressions and restricted cubic spline (RCS) analysis. To determine the relative importance of AVI in predicting CVD risk scores, random forest analysis was used. Results There was a significant positive correlation between AVI and FRS, China-PAR in all subgroup groups stratified by age, blood pressure and BMI. AVI showed higher importance in predicting CVD risk scores in FRS model, compared with these traditional risk factors. In China-PAR model, although AVI was not as predictive as SBP, it had better predictive power than many known risk factors such as lipids. Furthermore, AVI had significant J-shaped associations both with FRS and China-PAR scores. Conclusions AVI was significantly associated with CVD risk score. In FRS and China-PAR model, AVI showed relatively high importance in predicting CVD risk scores. These findings may support the use of arterial stiffness measurements in CVD risk assessment.
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Affiliation(s)
- Lin Jin
- Department of Ultrasound, Jiading Branch of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Ultrasound, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jianxiong Chen
- Department of Ultrasound, Mindong Hospital Affiliated to Fujian Medical University, Ningde, China
| | - Lingheng Wu
- Department of Ultrasound, Mindong Hospital Affiliated to Fujian Medical University, Ningde, China
| | - Mengjiao Zhang
- Department of Ultrasound, Jiading Branch of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jiali Sun
- Department of Ultrasound, Jiading Branch of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Cuiqin Shen
- Department of Ultrasound, Jiading Branch of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Lianfang Du
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Dingqian Wang
- School of Informatics, College of Science & Engineering, The University of Edinburgh, Edinburgh, United Kingdom
| | - Zhaojun Li
- Department of Ultrasound, Jiading Branch of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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14
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Davis MJ, Earley S, Li YS, Chien S. Vascular mechanotransduction. Physiol Rev 2023; 103:1247-1421. [PMID: 36603156 PMCID: PMC9942936 DOI: 10.1152/physrev.00053.2021] [Citation(s) in RCA: 98] [Impact Index Per Article: 49.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 09/26/2022] [Accepted: 10/04/2022] [Indexed: 01/07/2023] Open
Abstract
This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), including their sensing of mechanical stimuli and transduction of mechanical signals that result in the acute functional modulation and longer-term transcriptomic and epigenetic regulation of blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures and receptors, and junction proteins. The mechanosignaling pathways presented include the cytoskeleton, integrins, extracellular matrix, and intracellular signaling molecules. These are followed by discussions on mechanical regulation of transcriptome and epigenetics, relevance of mechanotransduction to health and disease, and interactions between VSMCs and ECs. Throughout this review, we offer suggestions for specific topics that require further understanding. In the closing section on conclusions and perspectives, we summarize what is known and point out the need to treat the vasculature as a system, including not only VSMCs and ECs but also the extracellular matrix and other types of cells such as resident macrophages and pericytes, so that we can fully understand the physiology and pathophysiology of the blood vessel as a whole, thus enhancing the comprehension, diagnosis, treatment, and prevention of vascular diseases.
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Affiliation(s)
- Michael J Davis
- Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri
| | - Scott Earley
- Department of Pharmacology, University of Nevada, Reno, Nevada
| | - Yi-Shuan Li
- Department of Bioengineering, University of California, San Diego, California
- Institute of Engineering in Medicine, University of California, San Diego, California
| | - Shu Chien
- Department of Bioengineering, University of California, San Diego, California
- Institute of Engineering in Medicine, University of California, San Diego, California
- Department of Medicine, University of California, San Diego, California
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15
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Walser M, Schlichtiger J, Dalla-Pozza R, Mandilaras G, Tengler A, Ulrich S, Oberhoffer FS, Oberhoffer-Fritz R, Böhm B, Haas NA, Jakob A. Oscillometric pulse wave velocity estimated via the Mobil-O-Graph shows excellent accuracy in children, adolescents and young adults: an invasive validation study. J Hypertens 2023; 41:597-607. [PMID: 36723480 DOI: 10.1097/hjh.0000000000003374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
AIMS Increased arterial stiffness, measured as arterial pulse wave velocity (PWV) is associated with an elevated cardiovascular risk. Although noninvasive PWV measurement methods have been validated by invasive measurement, there is little such data on pediatric patients. The purpose of this study was to 'fill the gap' by validating PWV obtained by Mobil-O-Graph in children, adolescents in comparison to young adults. METHODS Sixty patients (25 male, mean age 16.6 years; range 3-35 years) were included in this study. Fifty-one patients underwent cardiac catheterization after a heart transplantation (HTX) and nine for interventional atrial septal defect-closure. Specific invasive pulse wave velocities were assessed for the ascending aorta (aPWV) and entire central aorta (cPWV). These invasive PWV results were compared to simultaneously measured brachial cuff readings using Mobil-O-Graph (oPWV) stratified by age in two groups (PEDIATRICS <18 years|ADULTS ≥18 years). RESULTS Correlation analysis showed a positive linear relation between both invasive PWV measurements and the oPWV in all ages (cPWV/oPWV: r = 0.417, aPWV/oPWV: r = 0.628; P < 0.001). The oPWV data agreed better with the aPWV in mean-value comparisons and correlations with mean difference in PEDIATRICS was 0.41 ± 0.41 m/s (95% confidence interval 0.27-0.55). We also found the cPWV to be faster than the aPWV particularly in adults. In addition, cPWV correlated closer with age ( r = 0.393, P < 0.05). CONCLUSION Estimated oPWV using the Mobil-O-Graph demonstrated excellent accuracy in adults and pediatric patients. Therefore, the Mobil-O-Graph can be implemented as an ambulatory PWV measuring tool for pediatric cardiovascular risk stratification. CLINICAL TRIAL REGISTRATION German clinical trial registration, DRKS00015066.
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Affiliation(s)
- Matthias Walser
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - Jenny Schlichtiger
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - Robert Dalla-Pozza
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - Guido Mandilaras
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - Anja Tengler
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - Sarah Ulrich
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - Felix Sebastian Oberhoffer
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - Renate Oberhoffer-Fritz
- Institute of Preventive Pediatrics, Faculty of Sport and Health Sciences, Technical University of Munich, Munich, Germany
| | - Birgit Böhm
- Institute of Preventive Pediatrics, Faculty of Sport and Health Sciences, Technical University of Munich, Munich, Germany
| | - Nikolaus A Haas
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
| | - André Jakob
- Department of Pediatric Cardiology and Pediatric Intensive Care, Ludwig-Maximilians-University of Munich
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16
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Bunet R, Roy-Cardinal MH, Ramani H, Cleret-Buhot A, Durand M, Chartrand-Lefebvre C, Routy JP, Thomas R, Trottier B, Ancuta P, Hanna DB, Landay AL, Cloutier G, Tremblay CL, El-Far M. Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis. Viruses 2023; 15:700. [PMID: 36992409 PMCID: PMC10052544 DOI: 10.3390/v15030700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/24/2023] [Accepted: 03/04/2023] [Indexed: 03/11/2023] Open
Abstract
Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic roles of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32β and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.
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Affiliation(s)
- Rémi Bunet
- Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
| | - Marie-Hélène Roy-Cardinal
- Laboratory of Biorheology and Medical Ultrasonics, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
| | - Hardik Ramani
- Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
| | - Aurélie Cleret-Buhot
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
| | - Madeleine Durand
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
- Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada
| | - Carl Chartrand-Lefebvre
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
- Département de Radiologie, Radio-Oncologie et Médecine Nucléaire, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada
| | - Jean-Pierre Routy
- Chronic Viral Illness Service, Division of Hematology, McGill University Health Centre, Montréal and Research Institute of McGill University Health Centre, Montréal, QC H4A 3J1, Canada
| | - Réjean Thomas
- Clinique Médicale l’Actuel, Montréal, QC H2L 4P9, Canada
| | - Benoît Trottier
- Centre de Médecine Urbaine du Quartier Latin, Montréal, QC H2L 4E9, Canada
| | - Petronela Ancuta
- Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
| | - David B. Hanna
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Alan L. Landay
- Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA
| | - Guy Cloutier
- Laboratory of Biorheology and Medical Ultrasonics, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
- Département de Radiologie, Radio-Oncologie et Médecine Nucléaire, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada
- Institut de Génie Biomédical, Université de Montréal, Montréal, QC H3T 1J4, Canada
| | - Cécile L. Tremblay
- Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
| | - Mohamed El-Far
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC H2X 0A9, Canada
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17
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Watanabe T, Sassi S, Ulziibayar A, Hama R, Kitsuka T, Shinoka T. The Application of Porous Scaffolds for Cardiovascular Tissues. Bioengineering (Basel) 2023; 10:236. [PMID: 36829730 PMCID: PMC9952004 DOI: 10.3390/bioengineering10020236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/03/2023] [Accepted: 02/06/2023] [Indexed: 02/12/2023] Open
Abstract
As the number of arteriosclerotic diseases continues to increase, much improvement is still needed with treatments for cardiovascular diseases. This is mainly due to the limitations of currently existing treatment options, including the limited number of donor organs available or the long-term durability of the artificial organs. Therefore, tissue engineering has attracted significant attention as a tissue regeneration therapy in this area. Porous scaffolds are one of the effective methods for tissue engineering. However, it could be better, and its effectiveness varies depending on the tissue application. This paper will address the challenges presented by various materials and their combinations. We will also describe some of the latest methods for tissue engineering.
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Affiliation(s)
- Tatsuya Watanabe
- Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Salha Sassi
- Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Anudari Ulziibayar
- Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Rikako Hama
- Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Takahiro Kitsuka
- Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA
| | - Toshiharu Shinoka
- Center for Regenerative Medicine, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Department of Surgery, Nationwide Children’s Hospital, Ohio State University, Columbus, OH 43205, USA
- Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children’s Hospital, Columbus, OH 43205, USA
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18
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Tap L, Corsonello A, Di Rosa M, Fabbietti P, Formiga F, Moreno-González R, Ärnlöv J, Carlsson AC, Polinder-Bos HA, Roller-Wirnsberger RE, Wirnsberger GH, Kostka T, Guligowska A, Artzi-Medvedik R, Yehoshua I, Weingart C, Sieber CC, Gil P, Lainez Martinez S, Lattanzio F, Mattace-Raso FUS. Inflammaging and Blood Pressure Profiles in Late Life: The Screening for CKD among Older People across Europe (SCOPE) Study. J Clin Med 2022; 11:7311. [PMID: 36555930 PMCID: PMC9785752 DOI: 10.3390/jcm11247311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 12/03/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is a marker for systemic inflammation. Since inflammation plays a relevant role in vascular aging, the aim of this study was to investigate whether NLR is associated with blood pressure profiles in older adults. This study was performed within the framework of the SCOPE study including 2461 outpatients aged 75 years and over. Mean blood pressure values, namely systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were investigated across tertiles of NLR. Change in blood pressure levels in 2 years of follow-up were compared across categories of baseline NLR. Data of 2397 individuals were used, of which 1854 individuals had hypertension. Mean values of blood pressure did not differ across categories of baseline NLR in individuals without hypertension. Individuals with hypertension with a high-range NLR had lower SBP and PP when compared to those in low-range NLR (mean difference SBP -2.94 mmHg, p = 0.032 and PP -2.55 mmHg, p = 0.030). Mean change in blood pressure in 2 years did only slightly differ in non-clinically relevant ranges, when compared across tertiles of baseline NLR. NLR as a marker of inflammaging was not associated with unfavorable blood pressure profiles in older individuals with or without hypertension.
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Affiliation(s)
- Lisanne Tap
- Department of Internal Medicine, Section of Geriatric Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
| | - Andrea Corsonello
- Italian National Research Center on Aging (INRCA), 60124 Ancona, Italy
| | - Mirko Di Rosa
- Italian National Research Center on Aging (INRCA), 60124 Ancona, Italy
| | - Paolo Fabbietti
- Italian National Research Center on Aging (INRCA), 60124 Ancona, Italy
| | - Francesc Formiga
- Geriatric Unit, Internal Medicine Department, Bellvitge University Hospital-IDIBELL-L’Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Rafael Moreno-González
- Geriatric Unit, Internal Medicine Department, Bellvitge University Hospital-IDIBELL-L’Hospitalet de Llobregat, 08907 Barcelona, Spain
| | - Johan Ärnlöv
- School of Health and Social Studies, Dalarna University, 791 31 Falun, Sweden
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Axel C. Carlsson
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, 171 77 Stockholm, Sweden
- Academic Primary Health Care Centre, Stockholm Region, 113 65 Stockholm, Sweden
| | - Harmke A. Polinder-Bos
- Department of Internal Medicine, Section of Geriatric Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
| | | | | | - Tomasz Kostka
- Department of Geriatrics, Healthy Ageing Research Centre, Medical University of Lodz, 90-549 Lodz, Poland
| | - Agnieszka Guligowska
- Department of Geriatrics, Healthy Ageing Research Centre, Medical University of Lodz, 90-549 Lodz, Poland
| | - Rada Artzi-Medvedik
- Department of Nursing, The Recanati School for Community Health Professions, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel
| | - Ilan Yehoshua
- Maccabi Healthcare Services, Southern Region, Tel Aviv 69978, Israel
| | - Christian Weingart
- Department of General Internal Medicine and Geriatrics, Krankenhaus Barmherzige Brüder Regensburg and Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, 93049 Regensburg, Germany
| | - Cornel C. Sieber
- Department of General Internal Medicine and Geriatrics, Krankenhaus Barmherzige Brüder Regensburg and Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, 93049 Regensburg, Germany
| | - Pedro Gil
- Department of Geriatric Medicine, Hospital Clinico San Carlos, 28040 Madrid, Spain
| | - Sara Lainez Martinez
- Department of Geriatric Medicine, Hospital Clinico San Carlos, 28040 Madrid, Spain
| | | | - Francesco U. S. Mattace-Raso
- Department of Internal Medicine, Section of Geriatric Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
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Abstract
PURPOSE OF REVIEW Aging is an important risk factor for cardiovascular disease and is associated with increased vessel wall stiffness. Pathophysiological stiffening, notably in arteries, disturbs the integrity of the vascular endothelium and promotes permeability and transmigration of immune cells, thereby driving the development of atherosclerosis and related vascular diseases. Effective therapeutic strategies for arterial stiffening are still lacking. RECENT FINDINGS Here, we overview the literature on age-related arterial stiffening, from patient-derived data to preclinical in-vivo and in-vitro findings. First, we overview the common techniques that are used to measure stiffness and discuss the observed stiffness values in atherosclerosis and aging. Next, the endothelial response to stiffening and possibilities to attenuate this response are discussed. SUMMARY Future research that will define the endothelial contribution to stiffness-related cardiovascular disease may provide new targets for intervention to restore endothelial function in atherosclerosis and complement the use of currently applied lipid-lowering, antihypertensive, and anti-inflammatory drugs.
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Affiliation(s)
- Aukie Hooglugt
- Amsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences
- Amsterdam UMC, VU University Medical Center, Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
| | - Olivia Klatt
- Amsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences
| | - Stephan Huveneers
- Amsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences
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20
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Prasad K. Involvement of AGE and Its Receptors in the Pathogenesis of Hypertension in Elderly People and Its Treatment. Int J Angiol 2022; 31:213-221. [PMID: 36588874 PMCID: PMC9803554 DOI: 10.1055/s-0042-1756175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Both systolic and diastolic blood pressures increase with age up to 50 to 60 years of age. After 60 years of age systolic pressure rises to 84 years of age but diastolic pressure remains stable or even decreases. In the oldest age group (85-99 years), the systolic blood pressure (SBP) is high and diastolic pressure (DBP) is the lowest. Seventy percent of people older than 65 years are hypertensive. This paper deals with the role of advanced glycation end products (AGE) and its cell receptor (RAGE) and soluble receptor (sRAGE) in the development of hypertension in the elderly population. Plasma/serum levels of AGE are higher in older people as compared with younger people. Serum levels of AGE are positively correlated with age, arterial stiffness, and hypertension. Low serum levels of sRAGE are associated with arterial stiffness and hypertension. Levels of sRAGE are negatively correlated with age and blood pressure. Levels of sRAGE are lower in patients with arterial stiffness and hypertension than patients with high levels of sRAGE. AGE could induce hypertension through numerous mechanisms including, cross-linking with collagen, reduction of nitric oxide, increased expression of endothelin-1, and transforming growth factor-β (TGF-β). Interaction of AGE with RAGE could produce hypertension through the generation of reactive oxygen species, increased sympathetic activity, activation of nuclear factor-kB, and increased expression of cytokines, cell adhesion molecules, and TGF- β. In conclusion, the AGE-RAGE axis could be involved in hypertension in elderly people. Treatment for hypertension in elderly people should be targeted at reduction of AGE levels in the body, prevention of AGE formation, degradation of AGE in vivo, downregulation of RAGE expression, blockade of AGE-RAGE interaction, upregulation of sRAGE expression, and use of antioxidants.
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Affiliation(s)
- Kailash Prasad
- Department of Physiology (APP), College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
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21
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Fabiani M, Asnakew BA, Bowie DC, Chism SM, Clements GM, Gardner JC, Islam SS, Rubenstein SL, Gratton G. A healthy mind in a healthy body: Effects of arteriosclerosis and other risk factors on cognitive aging and dementia. THE PSYCHOLOGY OF LEARNING AND MOTIVATION 2022; 77:69-123. [PMID: 37139101 PMCID: PMC10153623 DOI: 10.1016/bs.plm.2022.08.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
In this review we start from the assumption that, to fully understand cognitive aging, it is important to embrace a holistic view, integrating changes in bodily, brain, and cognitive functions. This broad view can help explain individual differences in aging trajectories and could ultimately enable prevention and remediation strategies. As the title of this review suggests, we claim that there are not only indirect but also direct effects of various organ systems on the brain, creating cascades of phenomena that strongly contribute to age-related cognitive decline. Here we focus primarily on the cerebrovascular system, because of its direct effects on brain health and close connections with the development and progression of Alzheimer's Disease and other types of dementia. We start by reviewing the main cognitive changes that are often observed in normally aging older adults, as well as the brain systems that support them. Second, we provide a brief overview of the cerebrovascular system and its known effects on brain anatomy and function, with a focus on aging. Third, we review genetic and lifestyle risk factors that may affect the cerebrovascular system and ultimately contribute to cognitive decline. Lastly, we discuss this evidence, review limitations, and point out avenues for additional research and clinical intervention.
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Affiliation(s)
- Monica Fabiani
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Bethlehem A. Asnakew
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Daniel C. Bowie
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Sydney M. Chism
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Grace M. Clements
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Jennie C. Gardner
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Samia S. Islam
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Samantha L. Rubenstein
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
| | - Gabriele Gratton
- Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL, United States
- Psychology Department, University of Illinois at Urbana-Champaign, Champaign, IL, United States
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22
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Alkahtani R. Molecular mechanisms underlying some major common risk factors of stroke. Heliyon 2022; 8:e10218. [PMID: 36060992 PMCID: PMC9433609 DOI: 10.1016/j.heliyon.2022.e10218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 05/10/2022] [Accepted: 08/04/2022] [Indexed: 11/25/2022] Open
Abstract
Ischemic and hemorrhagic strokes are the most common known cerebrovascular disease which can be induced by modifiable and non-modifiable risk factors. Age and race are the most common non-modifiable risk factors of stroke. However, hypertension, diabetes, obesity, dyslipidemia, physical inactivity, and cardiovascular disorders are major modifiable risk factors. Understanding the molecular mechanism mediating each of these risk factors is expected to contribute significantly to reducing the risk of stroke, preventing neural damage, enhancing rehabilitation, and designing suitable treatments. Abnormalities in the structure of the blood-brain barrier and blood vessels, thrombosis, vasoconstriction, atherosclerosis, reduced cerebral blood flow, neural oxidative stress, inflammation, and apoptosis, impaired synaptic transmission, excitotoxicity, altered expression/activities of many channels and signaling proteins are the most knows mechanisms responsible for stroke induction. However, the molecular role of risk factors in each of these mechanisms is not well understood and requires a lot of search and reading. This review was designed to provide the reader with a single source of information that discusses the current update of the prevalence, pathophysiology, and all possible molecular mechanisms underlying some major risk factors of stroke namely, hypertension, diabetes mellitus, dyslipidemia, and lipid fraction, and physical inactivity. This provides a full resource for understanding the molecular effect of each of these risk factors in stroke.
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Affiliation(s)
- Reem Alkahtani
- Department of Basic Medical Sciences, College of Medicine at King Saud, Abdulaziz, University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
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23
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Wang M, Su W, Jiang CY, Li WP, Chen H, Li HW. Association Between Pulse Pressure With All-Cause and Cardiac Mortality in Acute Coronary Syndrome: An Observational Cohort Study. Front Cardiovasc Med 2022; 9:930755. [PMID: 35911514 PMCID: PMC9325995 DOI: 10.3389/fcvm.2022.930755] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/20/2022] [Indexed: 12/14/2022] Open
Abstract
BackgroundPulse pressure (PP) is a surrogate of aortic stiffness, and reflects cardiac performance and stroke volume. Previous studies have indicated that PP was a robust predictor of cardiovascular outcomes and mortality. However, results have been mixed, and very few studies have focused on the association of PP with mortality in acute coronary syndrome (ACS). Thus, we aimed to investigate the relationship between admission PP and the prognosis of patients with ACS.MethodsThis cohort study included 10,824 patients diagnosed with ACS from the Cardiovascular Center Beijing Friendship Hospital Database Bank (CBDBANK) from January 2013 to October 2018. Patients with cardiogenic shock, malignancy, severe trauma and, no PP at admission were excluded. Restricted cubic spline and Cox proportional hazards regression were used to evaluate the association between PP and 1-year all-cause and cardiac mortality.ResultsIn the whole cohort, a total of 237 (2.19%) all-cause deaths were reported at 1-year follow-up. Restricted cubic spline analysis suggested a J-shaped relationship between PP and mortality. Among patients with ACS, both lower and higher PP levels were related to an increased risk of mortality (Pnon–linear < 0.001); with a PP level of 30 or 80 mmHg, as compared with 50 mmHg, the adjusted hazard ratios for 1-year all-cause mortality were 2.02 (95% CI, 1.27–3.22) and 1.62 (95% CI, 1.13–2.33), respectively, after adjustments for potential confounders. Similar results were observed for cardiac deaths. The J-shaped relationship between PP and mortality remained in a series of subgroup analyses.ConclusionOur results suggested that both low and high PP were associated with an increased risk of mortality in patients with ACS.
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Affiliation(s)
- Man Wang
- Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wen Su
- Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Chun-Yan Jiang
- Department of Internal Medicine and Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Wei-Ping Li
- Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Chen
- Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hong-Wei Li
- Department of Cardiology, Cardiovascular Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease, Beijing, China
- *Correspondence: Hong-Wei Li,
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24
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Manoj R, Raj Kiran V, Nabeel PM, Sivaprakasam M, Joseph J. Evaluation of Pulse Contour Markers using an A-Mode Ultrasound: Association with Carotid Stiffness Markers and Ageing. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2022; 2022:4010-4013. [PMID: 36085673 DOI: 10.1109/embc48229.2022.9871405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Vascular ageing is directly associated with the blood vessel wall structural and functional abnormalities. Pulse morphology carries information on these abnormalities, and pulse contour analysis (PCA) identifies key amplitudes and timing information on the pulse waveforms that has a prognostic value towards cardiovascular risk stratification. PCA markers derived from second derivative waveforms represent the accelerative and decelerative phase of an arterial pulse. In this work, second derivative diameter waveforms of central arteries such as carotid artery are obtained using an A-mode ultrasound device. The derived PCA markers (b/a, c/a, d/a, e/a, (b-c-d-e)/a) from diameter waveform is investigated for its association with central stiffness markers and aging. An observational and cross-sectional study on 106 subjects (51 male/55 females) was conducted for this investigation. The highest correlation (r = 0.5, P < 0.001) was observed between c/a and PWV, and the lowest correlation was between c/a and AC. Group average values of PCA markers for each age decade group were correlated strongly (r > 0.9, p < 0.001) with age. A change > 19% was observed between the group average values of PCA markers of the normotensive and hypertensive population. The applicability of aforesaid PCA markers on central pulse waveforms, measured using a noninvasive device in resource-limited field settings, would accelerate such large scale vascular screening that is essential to understanding the cardiovascular risks at a population level. Clinical Relevance- This study provides an investigation into using second derivative diameter waveforms obtained from the carotid artery to find its associations with arterial stiffness and ageing.
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25
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Kitsuka T, Hama R, Ulziibayar A, Matsuzaki Y, Kelly J, Shinoka T. Clinical Application for Tissue Engineering Focused on Materials. Biomedicines 2022; 10:1439. [PMID: 35740460 PMCID: PMC9220152 DOI: 10.3390/biomedicines10061439] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/11/2022] [Accepted: 06/15/2022] [Indexed: 11/16/2022] Open
Abstract
Cardiovascular-related medical conditions remain a significant cause of death worldwide despite the advent of tissue engineering research more than half a century ago. Although autologous tissue is still the preferred treatment, donor tissue is limited, and there remains a need for tissue-engineered vascular grafts (TEVGs). The production of extensive vascular tissue (>1 cm3) in vitro meets the clinical needs of tissue grafts and biological research applications. The use of TEVGs in human patients remains limited due to issues related to thrombogenesis and stenosis. In addition to the advancement of simple manufacturing methods, the shift of attention to the combination of synthetic polymers and bio-derived materials and cell sources has enabled synergistic combinations of vascular tissue development. This review details the selection of biomaterials, cell sources and relevant clinical trials related to large diameter vascular grafts. Finally, we will discuss the remaining challenges in the tissue engineering field resulting from complex requirements by covering both basic and clinical research from the perspective of material design.
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Affiliation(s)
- Takahiro Kitsuka
- Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (T.K.); (R.H.); (A.U.); (Y.M.); (J.K.)
| | - Rikako Hama
- Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (T.K.); (R.H.); (A.U.); (Y.M.); (J.K.)
- Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-Cho, Koganei 184-8588, Japan
| | - Anudari Ulziibayar
- Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (T.K.); (R.H.); (A.U.); (Y.M.); (J.K.)
| | - Yuichi Matsuzaki
- Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (T.K.); (R.H.); (A.U.); (Y.M.); (J.K.)
| | - John Kelly
- Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (T.K.); (R.H.); (A.U.); (Y.M.); (J.K.)
| | - Toshiharu Shinoka
- Center for Regenerative Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; (T.K.); (R.H.); (A.U.); (Y.M.); (J.K.)
- Department of Cardiothoracic Surgery, Nationwide Children’s Hospital, Columbus, OH 43205, USA
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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26
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Serum Osteopontin Level Is Positively Associated with Aortic Stiffness in Patients with Peritoneal Dialysis. Life (Basel) 2022; 12:life12030397. [PMID: 35330148 PMCID: PMC8951753 DOI: 10.3390/life12030397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/04/2022] [Accepted: 03/07/2022] [Indexed: 12/26/2022] Open
Abstract
Background: Osteopontin (OPN) is regarded as a proinflammatory and proatherogenic molecule related to atherosclerosis. We aimed to evaluate the relationship between serum OPN and aortic stiffness (AS) of peritoneal dialysis (PD) patients. Methods: OPN and carotid-femoral pulse wave velocity (cfPWV) were measured by a commercial enzyme-linked immunosorbent assay kit and a validated tonometry system, respectively. Patients with cfPWV > 10 m/s were designated into the AS group. Results: Twenty-two patients (31.4%) were segregated into the AS group. Multivariate linear and logistic regression analysis showed that OPN was significantly related to cfPWV and was an independent predictor of AS. The receiver operating characteristic curve analysis showed that OPN was correlated with AS with an area under the curve of 0.903 (95% CI 0.809−0.961, p < 0.001). Conclusions: For PD patients, the serum OPN level was correlated with cfPWV and could play an important role in the process of AS.
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Siddiqui HB, Dogru S, Lashkarinia SS, Pekkan K. Soft-Tissue Material Properties and Mechanogenetics during Cardiovascular Development. J Cardiovasc Dev Dis 2022; 9:jcdd9020064. [PMID: 35200717 PMCID: PMC8876703 DOI: 10.3390/jcdd9020064] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 01/22/2022] [Accepted: 01/28/2022] [Indexed: 12/17/2022] Open
Abstract
During embryonic development, changes in the cardiovascular microstructure and material properties are essential for an integrated biomechanical understanding. This knowledge also enables realistic predictive computational tools, specifically targeting the formation of congenital heart defects. Material characterization of cardiovascular embryonic tissue at consequent embryonic stages is critical to understand growth, remodeling, and hemodynamic functions. Two biomechanical loading modes, which are wall shear stress and blood pressure, are associated with distinct molecular pathways and govern vascular morphology through microstructural remodeling. Dynamic embryonic tissues have complex signaling networks integrated with mechanical factors such as stress, strain, and stiffness. While the multiscale interplay between the mechanical loading modes and microstructural changes has been studied in animal models, mechanical characterization of early embryonic cardiovascular tissue is challenging due to the miniature sample sizes and active/passive vascular components. Accordingly, this comparative review focuses on the embryonic material characterization of developing cardiovascular systems and attempts to classify it for different species and embryonic timepoints. Key cardiovascular components including the great vessels, ventricles, heart valves, and the umbilical cord arteries are covered. A state-of-the-art review of experimental techniques for embryonic material characterization is provided along with the two novel methods developed to measure the residual and von Mises stress distributions in avian embryonic vessels noninvasively, for the first time in the literature. As attempted in this review, the compilation of embryonic mechanical properties will also contribute to our understanding of the mature cardiovascular system and possibly lead to new microstructural and genetic interventions to correct abnormal development.
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Affiliation(s)
- Hummaira Banu Siddiqui
- Department of Mechanical Engineering, Koc University, Istanbul 34450, Turkey; (H.B.S.); (S.D.); (S.S.L.)
| | - Sedat Dogru
- Department of Mechanical Engineering, Koc University, Istanbul 34450, Turkey; (H.B.S.); (S.D.); (S.S.L.)
- Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
| | - Seyedeh Samaneh Lashkarinia
- Department of Mechanical Engineering, Koc University, Istanbul 34450, Turkey; (H.B.S.); (S.D.); (S.S.L.)
- Department of Bioengineering, Imperial College London, London SW7 2BX, UK
| | - Kerem Pekkan
- Department of Mechanical Engineering, Koc University, Istanbul 34450, Turkey; (H.B.S.); (S.D.); (S.S.L.)
- Correspondence: ; Tel.: +90-(533)-356-3595
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28
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Cardoso CRL, Salles GF. Prognostic Value of Changes in Aortic Stiffness for Cardiovascular Outcomes and Mortality in Resistant Hypertension: a Cohort Study. Hypertension 2022; 79:447-456. [PMID: 35020459 DOI: 10.1161/hypertensionaha.121.18498] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 11/18/2021] [Indexed: 11/16/2022]
Abstract
The prognostic importance of changes in aortic stiffness for the occurrence of adverse cardiovascular outcomes and mortality has never been investigated in patients with resistant hypertension. We aimed to evaluate it in a prospective cohort of 442 resistant hypertension individuals. Changes in aortic stiffness were assessed by 2 carotid-femoral pulse wave velocity (CF-PWV) measurements performed over a median time interval of 4.7 years. Multivariate Cox analysis examined the associations between changes in CF-PWV (evaluated as continuous variables and categorized into quartiles and as increased/persistently high or reduced/persistently low) and the occurrence of total cardiovascular events (CVEs), major adverse CVEs, and cardiovascular/all-cause mortalities. During a median follow-up of 4.1 years after the second CF-PWV measurement, there were 49 total CVEs (42 major adverse CVEs) and 53 all-cause deaths (32 cardiovascular). As continuous variables, increments in absolute and relative changes in CF-PWV were associated with higher risks of CVEs and major adverse CVEs occurrence, but not of mortality. Divided into quartiles of CF-PWV changes, risks increased in the third and fourth quartile subgroups in relation to the reference first quartile subgroup (those with greatest CF-PWV reductions) for all outcomes. Patients who either increased or persisted with high CF-PWV had excess risks of cardiovascular morbidity/mortality, with hazard ratios ranging from 2.7 to 3.0, in relation to those who reduced or persisted with low CF-PWV values. In conclusion, reducing or preventing progression of aortic stiffness was associated with significant cardiovascular protection in patients with resistant hypertension, suggesting that it may be an additional clinical target of antihypertensive treatment.
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Affiliation(s)
- Claudia R L Cardoso
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Brazil
| | - Gil F Salles
- Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Universidade Federal do Rio de Janeiro, Brazil
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29
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Badji A, Cohen-Adad J, Girouard H. Relationship Between Arterial Stiffness Index, Pulse Pressure, and Magnetic Resonance Imaging Markers of White Matter Integrity: A UK Biobank Study. Front Aging Neurosci 2022; 14:856782. [PMID: 35800980 PMCID: PMC9252854 DOI: 10.3389/fnagi.2022.856782] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 05/09/2022] [Indexed: 12/29/2022] Open
Abstract
Background Alzheimer's disease and dementia in general constitute one of the major public health problems of the 21st century. Research in arterial stiffness and pulse pressure (PP) play an important role in the quest to reduce the risk of developing dementia through controlling modifiable risk factors. Objective The aim of the study is to investigate the association between peripheral PP, arterial stiffness index (ASI) and brain integrity, and to discover if ASI is a better predictor of white matter integrity than peripheral PP. Materials and Methods 17,984 participants 63.09 ± 7.31 from the UK Biobank were used for this study. ASI was estimated using infrared light (photoplethysmography) and peripheral PP was calculated by subtracting the diastolic from the systolic brachial blood pressure value. Measure of fractional anisotropy (FA) was obtained from diffusion imaging to estimate white matter microstructural integrity. White matter hyperintensities were segmented from the combined T1 and T2-weighted FLAIR images as a measure of irreversible white matter damage. Results An important finding is that peripheral PP better predicts white matter integrity when compared to ASI. This finding is consistent until 75 years old. Interestingly, no significant relationship is found between either peripheral PP or ASI and white matter integrity after 75 years old. Conclusion These results suggest that ASI from plethysmography should not be used to estimate cerebrovascular integrity in older adults and further question the relationship between arterial stiffness, blood pressure, and white matter damage after the age of 75 years old.
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Affiliation(s)
- Atef Badji
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montréal, Montréal, QC, Canada.,Functional Neuroimaging Unit, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montréal, QC, Canada.,Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada
| | - Julien Cohen-Adad
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montréal, Montréal, QC, Canada.,Functional Neuroimaging Unit, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montréal, QC, Canada.,Mila - Quebec AI Institute, Montréal, QC, Canada
| | - Hélène Girouard
- Functional Neuroimaging Unit, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Montréal, QC, Canada.,Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.,Groupe de Recherche sur le Système Nerveux Central, Montréal, QC, Canada.,Centre Interdisciplinaire de Recherche sur le Cerveau et l'Apprentissage, Montréal, QC, Canada.,Groupe de Recherche Universitaire Sur le Médicament (GRUM), Montréal, QC, Canada
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30
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Plunde O, Franco-Cereceda A, Bäck M. Cardiovascular Risk Factors and Hemodynamic Measures as Determinants of Increased Arterial Stiffness Following Surgical Aortic Valve Replacement. Front Cardiovasc Med 2021; 8:754371. [PMID: 34957246 PMCID: PMC8692982 DOI: 10.3389/fcvm.2021.754371] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 11/11/2021] [Indexed: 12/12/2022] Open
Abstract
Valvular and arterial function are tightly intertwined, both in terms of structural changes and hemodynamics. While proximal valvulo-vascular coupling contributes to the cardiovascular consequences of aortic stenosis, less is known on how peripheral arterial stiffness relates to aortic valve disease. Previous studies have shown conflicting results regarding the impact of aortic valve replacement on arterial stiffness. The aim of the present study was therefore to determine predictors of arterial stiffness in patients with and without aortic valve disease undergoing cardiac surgery. Cardio ankle vascular index (CAVI) and carotid femoral pulse wave velocity (cfPWV) were measured to determine arterial stiffness the day before and 3 days after surgery for either ascending aortic or aortic valve disease. Stratification on indication for surgery revealed that CAVI was significantly lower in patients with aortic valve stenosis (n = 45) and aortic valve regurgitation (n=30) compared with those with isolated ascending aortic dilatation (n = 13). After surgery, a significant increased CAVI was observed in aortic stenosis (median 1.34, IQR 0.74-2.26, p < 0.001) and regurgitation (median 1.04, IQR 0.01-1.49, p = 0.003) patients while cfPWV was not significantly changed. Age, diabetes, low body mass index, low pre-operative CAVI, as well as changes in ejection time were independently associated with increased CAVI after surgery. The results of the present study suggest aortic valve disease as cause of underestimation of arterial stiffness when including peripheral segments. We report cardiovascular risk factors and pinpoint the hemodynamic aspect ejection time to be associated with increased CAVI after aortic valve surgery.
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Affiliation(s)
- Oscar Plunde
- Unit of Cardiovascular Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, Stockholm, Sweden
| | - Anders Franco-Cereceda
- Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, Stockholm, Sweden
- Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Magnus Bäck
- Unit of Cardiovascular Medicine, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- Theme Heart and Vessels, Division of Valvular and Coronary Disease, Karolinska University Hospital, Stockholm, Sweden
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31
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Gauci S, Young LM, White DJ, Reddan JM, Lassemillante AC, Meyer D, Pipingas A, Scholey A. Diet May Moderate the Relationship Between Arterial Stiffness and Cognitive Performance in Older Adults. J Alzheimers Dis 2021; 85:815-828. [PMID: 34864661 PMCID: PMC8842781 DOI: 10.3233/jad-210567] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Cognitive decline is influenced by various factors including diet, cardiovascular disease, and glucose control. However, the combined effect of these risk factors on cognitive performance is yet to be fully understood. OBJECTIVE The current study aimed to explore the inter-relationship between these risk factors and cognitive performance in older adults at risk of future cognitive decline. METHODS The sample comprised 163 (Age: M = 65.23 years, SD = 6.50) participants. Food Frequency Questionnaire data was used to score diet quality and adherence to the Western Style Diet (WSD) and Prudent Style Diet (PSD). Glucose control was gauged by serum levels of glycated hemoglobin (HbA1c) and arterial stiffness was measured using carotid to femoral pulse wave velocity. Cognitive performance was assessed using two subtests of the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and Rey's Verbal Learning Test (RVLT). RESULTS Diet quality, adherence to the WSD or PSD, and glucose control were not significantly related to cognitive outcomes. However, a significant negative association was found between arterial stiffness and the spatial working memory subtest of SUCCAB (β= -0.21, p < 0.05). Arterial stiffness also significantly interacted with the PSD to impact total recall (F change (1,134) = 5.37, p < 0.05) and the composite score of RVLT (F change (1,134) = 4.03, p < 0.05). CONCLUSION In this sample of older adults at risk of cognitive decline, diet alone was not found to predict cognitive performance; however, it was found to moderate the relationship between arterial stiffness and cognition.
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Affiliation(s)
- Sarah Gauci
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia.,Heart and Mind Research, School of Medicine, Deakin University, Barwon Health, Geelong, Australia
| | - Lauren M Young
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia.,Food and Mood Centre, School of Medicine, Deakin University, Barwon Health, Geelong, Australia
| | - David J White
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia
| | - Jeffery M Reddan
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia
| | - Annie-Claude Lassemillante
- Department of Nursing and Allied Health, Faculty of Health, Arts and Design, Swinburne University, Melbourne, VIC, Australia
| | - Denny Meyer
- Department of Health Science and Biostatistics, Centre for Mental Health, Swinburne University, Melbourne, VIC, Australia
| | - Andrew Pipingas
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia
| | - Andrew Scholey
- Centre for Human Psychopharmacology, Swinburne University, Melbourne, VIC, Australia.,Nutrition Dietetics and Food, School of Clinical Sciences, Monash University, Melbourne, Australia
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32
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Angoff R, Mosarla RC, Tsao CW. Aortic Stiffness: Epidemiology, Risk Factors, and Relevant Biomarkers. Front Cardiovasc Med 2021; 8:709396. [PMID: 34820427 PMCID: PMC8606645 DOI: 10.3389/fcvm.2021.709396] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 09/30/2021] [Indexed: 12/19/2022] Open
Abstract
Aortic stiffness (AoS) is a maladaptive response to hemodynamic stress and both modifiable and non-modifiable risk factors, and elevated AoS increases afterload for the heart. AoS is a non-invasive marker of cardiovascular health and metabolic dysfunction. Implementing AoS as a diagnostic tool is challenging as it increases with age and varies amongst races. AoS is associated with lifestyle factors such as alcohol and smoking, as well as hypertension and comorbid conditions including metabolic syndrome and its components. Multiple studies have investigated various biomarkers associated with increased AoS, and this area is of particular interest given that these markers can highlight pathophysiologic pathways and specific therapeutic targets in the future. These biomarkers include those involved in the inflammatory cascade, anti-aging genes, and the renin-angiotensin aldosterone system. In the future, targeting AoS rather than blood pressure itself may be the key to improving vascular health and outcomes. In this review, we will discuss the current understanding of AoS, measurement of AoS and the challenges in interpretation, associated biomarkers, and possible therapeutic avenues for modulation of AoS.
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Affiliation(s)
- Rebecca Angoff
- Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
| | - Ramya C Mosarla
- Division of Cardiology, Department of Medicine, New York University Langone Health, New York, NY, United States
| | - Connie W Tsao
- Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
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33
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Morgan EE, Morran MP, Horen NG, Weaver DA, Nestor-Kalinoski AL. RNO3 QTL Regulates Vascular Structure and Arterial Stiffness in the Spontaneously Hypertensive Rat. Physiol Genomics 2021; 53:534-545. [PMID: 34755572 PMCID: PMC9275012 DOI: 10.1152/physiolgenomics.00038.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Increased arterial stiffness is an independent risk factor for hypertension, stroke, and cardiovascular morbidity. Thus, understanding the factors contributing to vascular stiffness is of critical importance. Here, we used a rat model containing a known quantitative trait locus (QTL) on chromosome 3 (RNO3) for vasoreactivity to assess potential genetic elements contributing to blood pressure, arterial stiffness, and their downstream effects on cardiac structure and function. Although no differences were found in blood pressure at any time point between parental spontaneously hypertensive rats (SHRs) and congenic SHR.BN3 rats, the SHRs showed a significant increase in arterial stiffness measured by pulse wave velocity. The degree of arterial stiffness increased with age in the SHRs and was associated with compensatory cardiac changes at 16 wk of age, and decompensatory changes at 32 wk, with no change in cardiac structure or function in the SHR.BN3 hearts at these time points. To evaluate the arterial wall structure, we used multiphoton microscopy to quantify cells and collagen content within the adventitia and media of SHR and SHR.BN3 arteries. No difference in cell numbers or proliferation rates was found, although phenotypic diversity was characterized in vascular smooth muscle cells. Herein, significant anatomical and physiological differences related to arterial structure and cardiovascular tone including collagen, pulse wave velocity (PWV), left ventricular (LV) geometry and function, and vascular smooth muscle cell (VSMC) contractile apparatus proteins were associated with the RNO3 QTL, thus providing a novel platform for studying arterial stiffness. Future studies delimiting the RNO3 QTL could aid in identifying genetic elements responsible for arterial structure and function.
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Affiliation(s)
- Eric E Morgan
- Department of Surgery, University of Toledo, Toledo, Ohio, United States.,Advanced Microscopy and Imaging Center, University of Toledo, Toledo, OH, United States.,Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Michael P Morran
- Department of Surgery, University of Toledo, Toledo, Ohio, United States.,Advanced Microscopy and Imaging Center, University of Toledo, Toledo, OH, United States
| | - Nicholas G Horen
- Department of Medicine, University of Toledo, Toledo, Ohio, United States
| | - David A Weaver
- Department of Surgery, University of Toledo, Toledo, Ohio, United States.,Advanced Microscopy and Imaging Center, University of Toledo, Toledo, OH, United States
| | - Andrea L Nestor-Kalinoski
- Department of Surgery, University of Toledo, Toledo, Ohio, United States.,Advanced Microscopy and Imaging Center, University of Toledo, Toledo, OH, United States
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34
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Youwakim J, Girouard H. Inflammation: A Mediator Between Hypertension and Neurodegenerative Diseases. Am J Hypertens 2021; 34:1014-1030. [PMID: 34136907 DOI: 10.1093/ajh/hpab094] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 05/03/2021] [Accepted: 06/15/2021] [Indexed: 12/14/2022] Open
Abstract
Hypertension is the most prevalent and modifiable risk factor for stroke, vascular cognitive impairment, and Alzheimer's disease. However, the mechanistic link between hypertension and neurodegenerative diseases remains to be understood. Recent evidence indicates that inflammation is a common pathophysiological trait for both hypertension and neurodegenerative diseases. Low-grade chronic inflammation at the systemic and central nervous system levels is now recognized to contribute to the physiopathology of hypertension. This review speculates that inflammation represents a mediator between hypertension and neurodegenerative diseases, either by a decrease in cerebral blood flow or a disruption of the blood-brain barrier which will, in turn, let inflammatory cells and neurotoxic molecules enter the brain parenchyma. This may impact brain functions including cognition and contribute to neurodegenerative diseases. This review will thus discuss the relationship between hypertension, systemic inflammation, cerebrovascular functions, neuroinflammation, and brain dysfunctions. The potential clinical future of immunotherapies against hypertension and associated cerebrovascular risks will also be presented.
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Affiliation(s)
- Jessica Youwakim
- Département de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, Canada
- Centre interdisciplinaire de recherche sur le cerveau et l’apprentissage (CIRCA); Montreal, QC, Canada
- Groupe de Recherche sur le Système Nerveux Central, Montreal, QC, Canada
| | - Hélène Girouard
- Département de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, Canada
- Centre interdisciplinaire de recherche sur le cerveau et l’apprentissage (CIRCA); Montreal, QC, Canada
- Groupe de Recherche sur le Système Nerveux Central, Montreal, QC, Canada
- Centre de recherche de l’Institut Universitaire de Gériaterie de Montréal, Montreal, QC, Canada
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35
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Inducible Prmt1 ablation in adult vascular smooth muscle leads to contractile dysfunction and aortic dissection. Exp Mol Med 2021; 53:1569-1579. [PMID: 34635781 PMCID: PMC8568946 DOI: 10.1038/s12276-021-00684-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/26/2021] [Accepted: 08/06/2021] [Indexed: 01/27/2023] Open
Abstract
Vascular smooth muscle cells (VSMCs) have remarkable plasticity in response to diverse environmental cues. Although these cells are versatile, chronic stress can trigger VSMC dysfunction, which ultimately leads to vascular diseases such as aortic aneurysm and atherosclerosis. Protein arginine methyltransferase 1 (Prmt1) is a major enzyme catalyzing asymmetric arginine dimethylation of proteins that are sources of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. Although a potential role of Prmt1 in vascular pathogenesis has been proposed, its role in vascular function has yet to be clarified. Here, we investigated the role and underlying mechanism of Prmt1 in vascular smooth muscle contractility and function. The expression of PRMT1 and contractile-related genes was significantly decreased in the aortas of elderly humans and patients with aortic aneurysms. Mice with VSMC-specific Prmt1 ablation (smKO) exhibited partial lethality, low blood pressure and aortic dilation. The Prmt1-ablated aortas showed aortic dissection with elastic fiber degeneration and cell death. Ex vivo and in vitro analyses indicated that Prmt1 ablation significantly decreased the contractility of the aorta and traction forces of VSMCs. Prmt1 ablation downregulated the expression of contractile genes such as myocardin while upregulating the expression of synthetic genes, thus causing the contractile to synthetic phenotypic switch of VSMCs. In addition, mechanistic studies demonstrated that Prmt1 directly regulates myocardin gene activation by modulating epigenetic histone modifications in the myocardin promoter region. Thus, our study demonstrates that VSMC Prmt1 is essential for vascular homeostasis and that its ablation causes aortic dilation/dissection through impaired myocardin expression.
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36
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Lester GR, Abiusi FS, Bodner ME, Mittermaier PM, Cote AT. The Impact of Fitness Status on Vascular and Baroreceptor Function in Healthy Women and Men. J Vasc Res 2021; 59:16-23. [PMID: 34571505 DOI: 10.1159/000518985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 08/10/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Chronic endurance exercise training elicits desirable physiological adaptations in the cardiovascular system. The volume of exercise training required to generate healthy adaptations is unclear. This study assessed the effects of differing exercise training levels on arterial stiffness, compliance, and autonomic function. METHODS Eighty healthy adults (38.5 ± 9.7 years; 44% female) defined as endurance-trained (ET, n = 29), normally active (NA, n = 27), or inactive (IN, n = 24) participated. Cardiovascular markers, including hemodynamics, large arterial compliance and small arterial compliance (LAC and SAC), carotid-femoral pulse wave velocity (PWV), and spontaneous baroreceptor sensitivity (BRS) were assessed. RESULTS ET showed significantly greater LAC values (21.4 ± 6.5) than NA (16.9 ± 2.5; p = 0.002) and IN (14.7 ± 3.2 mL × mm Hg × 10; p = 0.028). Values for SAC and BRS were significantly higher in ET than IN (p < 0.001 and p = 0.028, respectively), but not NA. Compared to IN, PWV values for ET and NA were significantly lower (p < 0.003). After adjusting for covariates (age, sex, and SBP), significant associations with cardiovascular fitness status were noted for all markers but BRS. CONCLUSION Endurance exercise increases LAC likely due to high-volume training; however, lower volumes of physical activity may be sufficient to positively benefit vascular health overall.
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Affiliation(s)
- Garth R Lester
- Faculty of Natural & Applied Sciences, Trinity Western University, Langley, British Columbia, Canada
| | - Francesca S Abiusi
- Faculty of Natural & Applied Sciences, Trinity Western University, Langley, British Columbia, Canada
| | - Michael E Bodner
- School of Human Kinetics, Trinity Western University, Langley, British Columbia, Canada
| | - Peter M Mittermaier
- Faculty of Natural & Applied Sciences, Trinity Western University, Langley, British Columbia, Canada
| | - Anita T Cote
- School of Human Kinetics, Trinity Western University, Langley, British Columbia, Canada.,Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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37
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The Causal Relationship between Endothelin-1 and Hypertension: Focusing on Endothelial Dysfunction, Arterial Stiffness, Vascular Remodeling, and Blood Pressure Regulation. Life (Basel) 2021; 11:life11090986. [PMID: 34575135 PMCID: PMC8472034 DOI: 10.3390/life11090986] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/13/2021] [Accepted: 09/17/2021] [Indexed: 12/01/2022] Open
Abstract
Hypertension (HTN) is one of the most prevalent diseases worldwide and is among the most important risk factors for cardiovascular and cerebrovascular complications. It is currently thought to be the result of disturbances in a number of neural, renal, hormonal, and vascular mechanisms regulating blood pressure (BP), so crucial importance is given to the imbalance of a number of vasoactive factors produced by the endothelium. Decreased nitric oxide production and increased production of endothelin-1 (ET-1) in the vascular wall may promote oxidative stress and low-grade inflammation, with the development of endothelial dysfunction (ED) and increased vasoconstrictor activity. Increased ET-1 production can contribute to arterial aging and the development of atherosclerotic changes, which are associated with increased arterial stiffness and manifestation of isolated systolic HTN. In addition, ET-1 is involved in the complex regulation of BP through synergistic interactions with angiotensin II, regulates the production of catecholamines and sympathetic activity, affects renal hemodynamics and water–salt balance, and regulates baroreceptor activity and myocardial contractility. This review focuses on the relationship between ET-1 and HTN and in particular on the key role of ET-1 in the pathogenesis of ED, arterial structural changes, and impaired vascular regulation of BP. The information presented includes basic concepts on the role of ET-1 in the pathogenesis of HTN without going into detailed analyses, which allows it to be used by a wide range of specialists. Also, the main pathological processes and mechanisms are richly illustrated for better understanding.
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38
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Badji A, de la Colina AN, Boshkovski T, Sabra D, Karakuzu A, Robitaille-Grou MC, Gros C, Joubert S, Bherer L, Lamarre-Cliche M, Stikov N, Gauthier CJ, Cohen-Adad J, Girouard H. A Cross-Sectional Study on the Impact of Arterial Stiffness on the Corpus Callosum, a Key White Matter Tract Implicated in Alzheimer's Disease. J Alzheimers Dis 2021; 77:591-605. [PMID: 32741837 DOI: 10.3233/jad-200668] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Vascular risk factors such as arterial stiffness play an important role in the etiology of Alzheimer's disease (AD), presumably due to the emergence of white matter lesions. However, the impact of arterial stiffness to white matter structure involved in the etiology of AD, including the corpus callosum remains poorly understood. OBJECTIVE The aims of the study are to better understand the relationship between arterial stiffness, white matter microstructure, and perfusion of the corpus callosum in older adults. METHODS Arterial stiffness was estimated using the gold standard measure of carotid-femoral pulse wave velocity (cfPWV). Cognitive performance was evaluated with the Trail Making Test part B-A. Neurite orientation dispersion and density imaging was used to obtain microstructural information such as neurite density and extracellular water diffusion. The cerebral blood flow was estimated using arterial spin labelling. RESULTS cfPWV better predicts the microstructural integrity of the corpus callosum when compared with other index of vascular aging (the augmentation index, the systolic blood pressure, and the pulse pressure). In particular, significant associations were found between the cfPWV, an alteration of the extracellular water diffusion, and a neuronal density increase in the body of the corpus callosum which was also correlated with the performance in cognitive flexibility. CONCLUSION Our results suggest that arterial stiffness is associated with an alteration of brain integrity which impacts cognitive function in older adults.
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Affiliation(s)
- Atef Badji
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.,Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.,Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.,Groupe de Recherche sur le Système Nerveux Central (GRSNC), Université de Montréal, Montreal, QC, Canada.,Centre interdisciplinaire de recherche sur le cerveau et l'apprentissage (CIRCA), Université de Montréal, Montreal, QC, Canada
| | - Adrián Noriega de la Colina
- Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.,Department of Biomedical Sciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.,Groupe de Recherche sur le Système Nerveux Central (GRSNC), Université de Montréal, Montreal, QC, Canada.,Centre interdisciplinaire de recherche sur le cerveau et l'apprentissage (CIRCA), Université de Montréal, Montreal, QC, Canada
| | - Tommy Boshkovski
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada
| | - Dalia Sabra
- Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.,Department of Biomedical Sciences, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.,Montreal Heart Institute, Montreal, QC, Canada.,PERFORM Centre, Concordia University, Montreal, QC, Canada
| | - Agah Karakuzu
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.,Montreal Heart Institute, Montreal, QC, Canada
| | | | - Charley Gros
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada
| | - Sven Joubert
- Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.,Department of Psychology, Faculty of Arts and Sciences, Université de Montréal, Montreal, QC, Canada
| | - Louis Bherer
- Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.,Montreal Heart Institute, Montreal, QC, Canada.,Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada
| | - Maxime Lamarre-Cliche
- Institut de Recherches Cliniques de Montréal, Université de Montréal, Montreal, QC, Canada
| | - Nikola Stikov
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.,Montreal Heart Institute, Montreal, QC, Canada
| | - Claudine J Gauthier
- Montreal Heart Institute, Montreal, QC, Canada.,Physics Department, Concordia University, Montreal, QC, Canada.,PERFORM Centre, Concordia University, Montreal, QC, Canada
| | - Julien Cohen-Adad
- NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada.,Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.,Functional Neuroimaging Unit, Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Université de Montréal, Montreal, QC, Canada
| | - Hélène Girouard
- Centre de recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Montreal, QC, Canada.,Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.,Groupe de Recherche sur le Système Nerveux Central (GRSNC), Université de Montréal, Montreal, QC, Canada.,Centre interdisciplinaire de recherche sur le cerveau et l'apprentissage (CIRCA), Université de Montréal, Montreal, QC, Canada
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Kim SH, Monticone RE, McGraw KR, Wang M. Age-associated proinflammatory elastic fiber remodeling in large arteries. Mech Ageing Dev 2021; 196:111490. [PMID: 33839189 PMCID: PMC8154723 DOI: 10.1016/j.mad.2021.111490] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 03/24/2021] [Accepted: 04/05/2021] [Indexed: 12/12/2022]
Abstract
Elastic fibers are the main components of the extracellular matrix of the large arterial wall. Elastic fiber remodeling is an intricate process of synthesis and degradation of the core elastin protein and microfibrils accompanied by the assembly and disassembly of accessory proteins. Age-related morphological, structural, and functional proinflammatory remodeling within the elastic fiber has a profound effect upon the integrity, elasticity, calcification, amyloidosis, and stiffness of the large arterial wall. An age-associated increase in arterial stiffness is a major risk factor for the pathogenesis of diseases of the large arteries such as hypertensive and atherosclerotic vasculopathy. This mini review is an update on the key molecular, cellular, functional, and structural mechanisms of elastic fiber proinflammatory remodeling in large arteries with aging. Targeting structural and functional integrity of the elastic fiber may be an effective approach to impede proinflammatory arterial remodeling with advancing age.
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Affiliation(s)
- Soo Hyuk Kim
- Laboratory of Cardiovascular Science, Intramural Research Program, National Institution on Aging, National Institutes of Health, Biomedical Research Center (BRC), 251 Bayview Boulevard, Baltimore, MD, 21224, USA
| | - Robert E Monticone
- Laboratory of Cardiovascular Science, Intramural Research Program, National Institution on Aging, National Institutes of Health, Biomedical Research Center (BRC), 251 Bayview Boulevard, Baltimore, MD, 21224, USA
| | - Kimberly R McGraw
- Laboratory of Cardiovascular Science, Intramural Research Program, National Institution on Aging, National Institutes of Health, Biomedical Research Center (BRC), 251 Bayview Boulevard, Baltimore, MD, 21224, USA
| | - Mingyi Wang
- Laboratory of Cardiovascular Science, Intramural Research Program, National Institution on Aging, National Institutes of Health, Biomedical Research Center (BRC), 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
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40
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Gao J, Lee J, Phan A, Fowlkes JB. Velocity Vector Imaging to Assess Longitudinal Wall Motion of Adult Carotid Arteries. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2021; 40:1195-1207. [PMID: 32914417 DOI: 10.1002/jum.15501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 08/08/2020] [Accepted: 08/15/2020] [Indexed: 06/11/2023]
Abstract
OBJECTIVE We aimed to assess longitudinal wall motion of the common carotid artery (CCA) using velocity vector imaging (VVI). METHODS From October 2018 to July 2019, we prospectively performed VVI of 204 CCAs (102 adult volunteers, 57 men, 45 women) in young (n = 40, 20-44 y), mid-age (n = 30, 45-64 y), and senior (n = 32, ≥65 y) groups. VVI parameters of CCA included longitudinal motion pattern, motion parameters (strain, strain rate, displacement), and time-to-peak motion parameters (time-to-peak strain, time-to-peak strain rate, time-to-peak displacement). Statistical analyses included one-way ANOVA post-hoc testing to examine the difference in VVI parameters among the 3 age groups and in paired groups; unpaired t tests to examine the difference in VVI parameters between CCAs with and without atherosclerotic plaque, between hypertensive and normotensive subjects without atherosclerotic plaque; linear regression to analyze correlations of VVI parameters to age, carotid intima-media thickness; and intraclass correlation coefficient to test inter- and intra-observer reliability in performing VVI of the CCA. RESULTS Differences in VVI parameters and patterns among the 3 age groups, between hypertensive and normotensive, and CCAs with and without plaque were significant (p < .01). CCA motion- and time-to-peak motion parameters were correlated to age (R2 = 0.63-0.56) and carotid intima-media thickness (R2 = 0.29-0.22). CCA wall motion dyssynchrony was remarkable in seniors. The repeatability and reproducibility for performing carotid artery VVI were good (intraclass correlation coefficient > 0.85). CONCLUSIONS VVI is feasible to assess changes in longitudinal CCA wall mechanical properties and synchrony with aging, atherosclerosis, and hypertension.
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Affiliation(s)
- Jing Gao
- Rocky Vista University, Ivins, Utah
- Weill Cornell Medicine, Cornell University, New York, New York
| | | | | | - J Brian Fowlkes
- Department of Radiology, University of Michigan, Ann Arbor, Michigan
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41
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Zhu Y, Reinach PS, Ge C, Li Y, Wu B, Xie Q, Tong L, Chen W. Corneal Collagen Cross-Linking Pretreatment Mitigates Injury-Induced Inflammation, Hemangiogenesis and Lymphangiogenesis In Vivo. Transl Vis Sci Technol 2021; 10:11. [PMID: 34550310 PMCID: PMC8475280 DOI: 10.1167/tvst.10.5.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Purpose The purpose of this study was to evaluate if corneal collagen cross-linking (CXL) pretreatment dampens suture-induced hemangiogenesis and lymphangiogenesis driven by inflammation. Methods Four weeks after CXL pretreatment, suture emplacement was performed in rats. The time dependent effects were compared of this procedure in three groups: (1) suture-induced neovascularization (SNV group); (2) CXL treatment prior to suture-induced neovascularization (CXL + SNV group); (3) Normal control (NC group). Serial morphometric measurements evaluated suture-induced hemangiogenesis and lymphangiogenesis. CD45 and CD68 immunofluorescent staining pattern changes determined immune cell activation, stromal leucocyte, and macrophage infiltration. The real-time quantitative polymerase chain reaction (RT-qPCR) determined angiogenic and lymphangiogenic gene expression level changes. Western blots evaluated protein expression levels of vascular endothelial cell CD31 and lymphatic vessel endothelial hyaluronan receptor (LYVE-1). Results On days 7 and 14 after suture emplacement, the rises in angiogenesis, lymphangiogenesis, CD45+ and CD68+ cell infiltration were less in the CXL pretreated (CXL + SNV) group than in the untreated (SNV) group. Angiogenic and lymphangiogenic mRNA levels and CD31 and LYVE-1 protein and proinflammatory cytokines were also suppressed, confirming that CXL pretreatment improved the wound healing response. Conclusions CXL pretreatment inhibits injury-induced angiogenesis and lymphangiogenesis. These reductions suggest that prior CXL therapy decrease ocular inflammation reactivated by secondary trauma. Translational Relevance CXL pretreatment induces increases in stromal stiffness which in turn reduces trauma or microbial driven increases in inflammation, angiogenesis, and lymphangiogenesis. These beneficial effects suggest that this novel procedure may improve therapeutic management of trauma-induced corneal disease in a clinical setting.
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Affiliation(s)
- Yirui Zhu
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China.,Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, China
| | - Peter S Reinach
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China
| | - Chaoxiang Ge
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China
| | - Yun Li
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China
| | - Biao Wu
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China
| | - Qi Xie
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China
| | - Louis Tong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Singapore National Eye Centre, Singapore, Singapore.,Singapore Eye Research Institute, Singapore, Singapore.,Duke-NUS Medical School, Singapore, Singapore
| | - Wei Chen
- School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Zhejiang, China
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42
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Cismaru G, Serban T, Tirpe A. Ultrasound Methods in the Evaluation of Atherosclerosis: From Pathophysiology to Clinic. Biomedicines 2021; 9:418. [PMID: 33924492 PMCID: PMC8070406 DOI: 10.3390/biomedicines9040418] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 04/09/2021] [Accepted: 04/10/2021] [Indexed: 12/11/2022] Open
Abstract
Atherosclerosis is a key pathological process that causes a plethora of pathologies, including coronary artery disease, peripheral artery disease, and ischemic stroke. The silent progression of the atherosclerotic disease prompts for new surveillance tools that can visualize, characterize, and provide a risk evaluation of the atherosclerotic plaque. Conventional ultrasound methods-bright (B)-mode US plus Doppler mode-provide a rapid, cost-efficient way to visualize an established plaque and give a rapid risk stratification of the patient through the Gray-Weale standardization-echolucent plaques with ≥50% stenosis have a significantly greater risk of ipsilateral stroke. Although rather disputed, the measurement of carotid intima-media thickness (C-IMT) may prove useful in identifying subclinical atherosclerosis. In addition, contrast-enhanced ultrasonography (CEUS) allows for a better image resolution and the visualization and quantification of plaque neovascularization, which has been correlated with future cardiovascular events. Newly emerging elastography techniques such as strain elastography and shear-wave elastography add a new dimension to this evaluation-the biomechanics of the arterial wall, which is altered in atherosclerosis. The invasive counterpart, intravascular ultrasound (IVUS), enables an individualized assessment of the anti-atherosclerotic therapies, as well as a direct risk assessment of these lesions through virtual histology IVUS.
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Affiliation(s)
- Gabriel Cismaru
- Fifth Department of Internal Medicine, Cardiology-Rehabilitation, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Teodora Serban
- Medical Imaging Department, Iuliu Hatieganu University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania;
| | - Alexandru Tirpe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania
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43
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Huang SY, Wu DA, Tsai JP, Hsu BG. Serum Levels of Fibroblast Growth Factor 21 Are Positively Associated with Aortic Stiffness in Patients with Type 2 Diabetes Mellitus. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18073434. [PMID: 33810243 PMCID: PMC8037617 DOI: 10.3390/ijerph18073434] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 02/21/2021] [Accepted: 03/21/2021] [Indexed: 12/12/2022]
Abstract
Aortic stiffness (AS), assessed using carotid–femoral pulse wave velocity (cfPWV), is associated with cardiovascular disease in type 2 diabetes mellitus (T2DM). The relationship between serum fibroblast growth factor 21 (FGF-21) and AS in T2DM patients was evaluated. Fasting serum FGF-21 levels of 130 T2DM patients were measured using an enzyme immunoassay kit. A validated tonometry system was used to measure cfPWV (>10 m/s indicated AS). Of these T2DM patients, 34.6% were defined as the AS group. T2DM patients with AS were older; exhibited higher systolic blood pressure, diastolic blood pressure, and body fat mass; higher triglyceride, fasting glucose, glycosylated hemoglobin, and creatinine levels; higher urine albumin-to-creatinine ratios and serum FGF-21 levels; and lower estimated glomerular filtration rates. The FGF-21 level (odds ratio = 1.005, 95% confidence interval: 1.002–1.009, p = 0.002) as well as systolic blood pressure was an independent predictor of AS and positively correlated to cfPWV values (β = 0.369, p < 0.001) in T2DM patients. For T2DM patients, serum FGF-21 level could be a predictor for AS.
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Affiliation(s)
- Sin-Yi Huang
- Department of General Practice, Far Eastern Memorial Hospital, New Taipei City 22016, Taiwan;
| | - Du-An Wu
- School of Medicine, Tzu-Chi University, Hualien 970374, Taiwan;
- Division of Metabolism and Endocrinology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan
| | - Jen-Pi Tsai
- School of Medicine, Tzu-Chi University, Hualien 970374, Taiwan;
- Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan
- Correspondence: (J.-P.T.); (B.-G.H.)
| | - Bang-Gee Hsu
- School of Medicine, Tzu-Chi University, Hualien 970374, Taiwan;
- Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan
- Correspondence: (J.-P.T.); (B.-G.H.)
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Di Giuseppe M, Farzaneh S, Zingales M, Pasta S, Avril S. Patient-specific computational evaluation of stiffness distribution in ascending thoracic aortic aneurysm. J Biomech 2021; 119:110321. [PMID: 33662747 DOI: 10.1016/j.jbiomech.2021.110321] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 01/21/2021] [Accepted: 02/03/2021] [Indexed: 12/21/2022]
Abstract
Quantifying local aortic stiffness properties in vivo is acknowledged as essential to assess the severity of an ascending thoracic aortic aneurysm (ATAA). Recently, the LESI (local extensional stiffness identification) methodology has been established to quantify non-invasively local stiffness properties of ATAAs using electrocardiographic-gated computed tomography (ECG-gated CT) scans. The aim of the current study was to determine the most sensitive markers of local ATAA stiffness estimation with the hypothesis that direct measures of local ATAA stiffness could better detect the high-risk patients. A cohort of 30 patients (12 BAV and 18 TAV) referred for aortic size evaluation by ECG-gated CT were recruited. For each patient, the extensional stiffness Q was evaluated by the LESI methodology whilst computational flow analyses were also performed to derive hemodynamics markers such as the wall shear stress (WSS). A strong positive correlation was found between the extensional stiffness and the aortic pulse pressure (R = 0.644 and p < 0.001). Interestingly, a significant positive correlation was also found between the extensional stiffness and patients age for BAV ATAAs (R = 0.619 and p = 0.032), but not for TAV ATAAs (R = -0.117 and p = 0.645). No significant correlation was found between the extensional stiffness and WSS evaluated locally. There was no significant difference either in the extensional stiffness between BAV ATAAs and TAV ATAAs (Q = 3.6 ± 2.5 MPa.mm for BAV ATAAs vs Q = 5.3 ± 3.1 MPa.mm for TAV ATAAs, p = 0.094). Future work will focus on relating the extensional stiffness to the patient-specific rupture risk of ATAAs on larger cohorts to confirm the promising interest of the LESI methodology.
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Affiliation(s)
- Marzio Di Giuseppe
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90128 Palermo, Italy
| | - Solmaz Farzaneh
- Mines Saint-Etienne, Univ Lyon, Univ Jean Monnet, INSERM, U1059 SAINBIOSE, Saint-Étienne 42023, France
| | - Massimiliano Zingales
- Department of Engineering, Viale delle Scienze, Ed.8, University of Palermo, 90128 Palermo, Italy
| | - Salvatore Pasta
- Department of Engineering, Viale delle Scienze, Ed.8, University of Palermo, 90128 Palermo, Italy
| | - Stéphane Avril
- Mines Saint-Etienne, Univ Lyon, Univ Jean Monnet, INSERM, U1059 SAINBIOSE, Saint-Étienne 42023, France.
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45
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Adatia K, Newcombe VFJ, Menon DK. Contusion Progression Following Traumatic Brain Injury: A Review of Clinical and Radiological Predictors, and Influence on Outcome. Neurocrit Care 2021; 34:312-324. [PMID: 32462411 PMCID: PMC7253145 DOI: 10.1007/s12028-020-00994-4] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Secondary injuries remain an important cause of the morbidity and mortality associated with traumatic brain injury (TBI). Progression of cerebral contusions occurs in up to 75% of patients with TBI, and this contributes to subsequent clinical deterioration and requirement for surgical intervention. Despite this, the role of early clinical and radiological factors in predicting contusion progression remains relatively poorly defined due to studies investigating progression of all types of hemorrhagic injuries as a combined cohort. In this review, we summarize data from recent studies on factors which predict contusion progression, and the effect of contusion progression on clinical outcomes.
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Affiliation(s)
- Krishma Adatia
- Division of Anaesthesia, University of Cambridge, Cambridge, UK.
| | | | - David K Menon
- Division of Anaesthesia, University of Cambridge, Cambridge, UK
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46
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Li Y, Li R, Liu M, Nie Z, Muir ER, Duong TQ. MRI study of cerebral blood flow, vascular reactivity, and vascular coupling in systemic hypertension. Brain Res 2020; 1753:147224. [PMID: 33358732 DOI: 10.1016/j.brainres.2020.147224] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 09/30/2020] [Accepted: 11/27/2020] [Indexed: 01/14/2023]
Abstract
Chronic hypertension alters cerebrovascular function, which can lead to neurovascular pathologies and increased susceptibility to neurological disorders. The purpose of this study was to utilize in vivo MRI methods with corroborating immunohistology to evaluate neurovascular dysfunction due to progressive chronic hypertension. The spontaneously hypertensive rat (SHR) model at different stages of hypertension was studied to evaluate: i) basal cerebral blood flow (CBF), ii) cerebrovascular reactivity (CVR) assessed by CBF and blood-oxygenation level dependent (BOLD) signal changes to hypercapnia, iii) neurovascular coupling from CBF and BOLD changes to forepaw stimulation, and iv) damage of neurovascular unit (NVU) components (microvascular, astrocyte and neuron densities). Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR (mild hypertension), basal CBF was higher (p < 0.05), CVR trended higher, and neurovascular coupling response was higher (p < 0.05), compared to normotensive rats. In 40-week SHR (severe hypertension), basal CBF, CVR, and neurovascular coupling response were reversed to similar or below normotensive rats, and were significantly different from 10-week SHR (p < 0.05). Immunohistological analysis found significantly reduced microvascular density, increased astrocytes, and reduced neuronal density in SHR at 40 weeks (p < 0.05) but not at 10 weeks (p > 0.05) in comparison to age-matched controls. In conclusion, we observed a bi-phasic basal CBF, CVR and neurovascular coupling response from early to late hypertension using in vivo MRI, with significant changes prior to changes in the NVU components from histology. MRI provides clinically relevant data that might be useful to characterize neurovascular pathogenesis on the brain in hypertension.
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Affiliation(s)
- Yunxia Li
- Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Renren Li
- Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Meng Liu
- Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhiyu Nie
- Department of Neurology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
| | - Eric R Muir
- Department of Radiology, Renaissance School of Medicine, Stony Brook University Hospital, Stony Brook, NY, USA
| | - Tim Q Duong
- Department of Radiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA.
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Del Giorno R, Lavorato Hadjeres S, Stefanelli K, Allegra G, Zapparoli C, Predrag L, Berwert L, Gabutti L. Consequences of Supraphysiological Dialysate Magnesium on Arterial Stiffness, Hemodynamic Profile, and Endothelial Function in Hemodialysis: A Randomized Crossover Study Followed by a Non-Controlled Follow-Up Phase. Adv Ther 2020; 37:4848-4865. [PMID: 32996010 PMCID: PMC7595984 DOI: 10.1007/s12325-020-01505-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 09/12/2020] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Increasing dialysate magnesium (D-Mg2+) appears to be an intriguing strategy to obtain cardiovascular benefits in subjects with end-stage kidney disease (ESKD) on hemodialysis. To date, however, hemodialysis guidelines do not suggest to increase D-Mg2+ routinely set at 0.50 mmol/L. METHODS A randomized 4-week crossover study aimed at investigating the consequences of increasing D-Mg2+ from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis. The long-term effect of higher D-Mg2+ on mineral metabolism markers was investigated in a 6-month follow-up. Data were analyzed by linear mixed models for repeated measures. RESULTS Data of 39 patients were analyzed. Pulse wave velocity and pulse pressure significantly decreased on the higher D-Mg2+ compared with the standard one by - 0.91 m/s (95% confidence interval - 1.52 to - 0.29; p = 0.01) and - 9.61 mmHg (- 18.89 to - 0.33, p = 0.04), respectively. A significant reduction in systolic blood pressure of - 12.96 mmHg (- 24.71 to - 1.22, p = 0.03) was also observed. No period or carryover effects were observed. During the long-term follow-up phase the higher D-Mg2+ significantly increased ionized and total serum Mg (respectively from 0.54 to 0.64 and from 0.84 to 1.07 mmol/L; mean percentage change from baseline to follow-up + 21% and + 27%; p ≤ 0.001), while parathormone (PTH) decreased significantly (from 36.6 to 34.4 pmol/L; % change - 11%, p = 0.03). CONCLUSIONS Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of 0.75 mmol/L D-Mg2+ on major clinical outcomes. TRIAL REGISTRATION The study was retrospectively registered on the ISRCTN registry (ISRCTN 74139255) on 18 June 2020.
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Affiliation(s)
- Rosaria Del Giorno
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
- Institute of Biomedicine, University of Southern Switzerland, Lugano, Switzerland.
| | - Soraya Lavorato Hadjeres
- Nephrology and Dialysis Service, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Kevyn Stefanelli
- Department of Social Sciences and Economics, Sapienza University of Rome, Rome, Italy
| | - Giampiero Allegra
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Claudia Zapparoli
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Lazarevic Predrag
- Nephrology and Dialysis Service, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Lorenzo Berwert
- Nephrology and Dialysis Service, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Luca Gabutti
- Department of Internal Medicine, Clinical Research Unit, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
- Nephrology and Dialysis Service, Regional Hospital of Bellinzona and Valli, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
- Institute of Biomedicine, University of Southern Switzerland, Lugano, Switzerland.
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48
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Forte G, Casagrande M. Effects of Blood Pressure on Cognitive Performance in Aging: A Systematic Review. Brain Sci 2020; 10:E919. [PMID: 33261205 PMCID: PMC7760512 DOI: 10.3390/brainsci10120919] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 11/17/2020] [Accepted: 11/24/2020] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION Cognitive functions play a crucial role in daily functioning. Unfortunately, some cognitive abilities decline in the process of healthy aging. An increasing body of evidence has highlighted the role of lifestyle habits and cardiovascular diseases, such as high blood pressure, in increasing the risk of cognitive decline. Surprisingly, although hypertension is a modifiable risk factor for cerebrovascular damage, the role of hypertension on cognitive impairment development is not still clear. Several key questions remain unresolved, and there are many inconsistent results in studies considering this topic. This review is aimed to systematically analyze the results found by the studies that investigated whether high blood pressure, in both hypertensive and healthy people, is related to cognitive performance. Furthermore, it points to evaluate the role of age in this relationship. Method: The review process was conducted according to the PRISMA statement. Restrictions were made, selecting the studies in English and published in peer-review journals, including at least one cognitive measure and blood pressure measurement. Studies that included participants with medical conditions, dementia, psychiatric disorders, strokes, and brain injury were excluded. Cross-sectional and longitudinal studies were analyzed separately. Finally, blood pressure measured at young life (18-39 years), midlife (age 40-64 years), elderly (65-74 years), and old age (≥75 years) were considered. Results: The review allows 68 studies to be selected, which include 154,935 participants. The results provided evidence of an adverse effect of exposure to high blood pressure on cognitive performance. High blood pressure in midlife was linked with poorer cognitive functioning; this evidence was found in cross-sectional and longitudinal studies. However, this association declines with increasing age and tends to become inconsistent. In older people, the relationship between blood pressure and cognitive performance is non-linear, highlighting a beneficial effect of high blood pressure on cognition. Conclusions: Despite some limitations, this review showed that cardiovascular and neuro-cognitive systems do not operate in isolation, but they are related. Blood pressure can be considered an early biomarker of cognitive impairment, and the necessity of early blood pressure measurement and control was underlined.
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Affiliation(s)
- Giuseppe Forte
- Dipartimento di Psicologia, Università di Roma “Sapienza”, 00185 Rome, Italy
| | - Maria Casagrande
- Dipartimento di Psicologia Dinamica e Clinica, Università di Roma “Sapienza”, 00185 Rome, Italy;
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Kaolawanich Y, Boonyasirinant T. Impact of aortic stiffness by velocity-encoded magnetic resonance imaging on late gadolinium enhancement to predict cardiovascular events. INTERNATIONAL JOURNAL OF CARDIOLOGY. HEART & VASCULATURE 2020; 30:100635. [PMID: 33015313 PMCID: PMC7522332 DOI: 10.1016/j.ijcha.2020.100635] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/04/2020] [Accepted: 09/07/2020] [Indexed: 11/16/2022]
Abstract
Background Increased aortic stiffness has been established as a marker in various cardiovascular diseases. Previous reports revealed a significant correlation between aortic stiffness and myocardial scarring using the late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR). However, prognostic data concerning aortic stiffness combining myocardial scarring remains limited. Method A total of 402 patients who had undergone clinical CMR for the evaluation of cardiac function, LGE, and aortic pulse wave velocity (PWV) using velocity encoded-CMR (VE-CMR) were included. Patients were classified into 4 groups using mean PWV and the presence of LGE as elevated or non-elevated PWV and positive or negative LGE. Patients received follow-up for major adverse cardiovascular events (MACE) comprising cardiovascular death, non-fatal myocardial infarction, hospitalization for heart failure, coronary revascularization, and ischemic stroke. Predictors of MACE and hard cardiac events (cardiovascular death or non-fatal myocardial infarction) were evaluated. Results During the average follow-up period of 47.7 months, 58 MACE occurred. Patients who had elevated PWV and positive LGE experienced the highest rate of MACE compared to the group with non-elevated PWV and negative LGE (HR 11.90, p < 0.001). Among patients who had LGE, those who had elevated PWV experienced a 2.4-times higher rate of MACE compared to those who had non-elevated PWV. Multivariate analysis showed that PWV and LGE were independent predictors of MACE and hard cardiac events. PWV had excellent intra- and inter-observer reproducibility (intra-: ICC = 0.98, p < 0.001, inter-: ICC = 0.97, p < 0.001). Conclusion Aortic stiffness using VE-CMR had prognostic value to predict cardiovascular events, with the added benefits of LGE.
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Key Words
- Aortic stiffness
- CI, confidence interval
- CMR, cardiovascular magnetic resonance
- Cardiovascular magnetic resonance imaging
- FOV, field of view
- HR, hazard ratio
- LA, left atrial/atrium
- LGE, late gadolinium enhancement
- LVEF, left ventricular ejection fraction
- Late gadolinium enhancement
- MACE, major adverse cardiovascular events
- PWV, pulse wave velocity
- Prognosis
- SD, standard deviation
- STEMI, ST-elevation myocardial infarction
- T, tesla
- TE, echo time
- TR, repetition time
- VE, velocity-encoded
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Affiliation(s)
- Yodying Kaolawanich
- Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Thananya Boonyasirinant
- Division of Cardiology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Rooprai J, Boodhwani M, Beauchesne L, Chan KL, Dennie C, Nagpal S, Messika-Zeitoun D, Coutinho T. Thoracic Aortic Aneurysm Growth in Bicuspid Aortic Valve Patients: Role of Aortic Stiffness and Pulsatile Hemodynamics. J Am Heart Assoc 2020; 8:e010885. [PMID: 30966855 PMCID: PMC6507195 DOI: 10.1161/jaha.118.010885] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Background Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. A thoracic aortic aneurysm (TAA) is present in ≈50% of BAV patients, who also have an 8‐fold higher risk of aortic dissection than the general population. Because the health of the aorta is directly reflected in its stiffness and pulsatile hemodynamics, we hypothesized that measures of aortic stiffness and arterial load would be associated with TAA growth in BAV. Methods and Results Twenty‐nine unoperated participants with TAA due to BAV who had serial imaging were recruited. Aortic stiffness and steady and pulsatile arterial load were evaluated with validated methods that integrate arterial tonometry with echocardiography. TAA growth was assessed retrospectively based on available imaging, blinded to hemodynamic status. Multivariable linear regression assessed associations of aortic stiffness and hemodynamic variables with TAA growth, adjusting for potential confounders. Overall, 66% of participants were men. Mean±SD for age, baseline aneurysm size, growth rate, and follow‐up time were 57.2±8.3 years, 46.9±3.6 mm, 0.75±0.81 mm/y, and 2.9±3.3 years, respectively. We found that greater aortic stiffness (β±SE for carotid‐femoral pulse wave velocity: 0.30±0.13. P=0.03) and aortic characteristic impedance (β±SE: 0.46±0.18, P=0.02), as well as lower total arterial and proximal aortic compliance (β±SE: −0.44±0.21, P=0.05, and −0.63±0.16, P=0.001, respectively) were independently associated with faster aneurysm growth. Conclusions In patients with TAA due to BAV, measures of greater aortic stiffness and pulsatile arterial load indicate an association with accelerated aneurysm expansion. Assessing arterial hemodynamics may be useful for risk stratification and disease monitoring in TAA patients with BAV.
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Affiliation(s)
- Jasjit Rooprai
- 1 Faculty of Medicine University of Ottawa Ontario Canada
| | - Munir Boodhwani
- 2 Division of Cardiac Surgery University of Ottawa Heart Institute Ottawa Ontario Canada
| | - Luc Beauchesne
- 3 Division of Cardiology University of Ottawa Heart Institute Ottawa Ontario Canada
| | - Kwan-Leung Chan
- 3 Division of Cardiology University of Ottawa Heart Institute Ottawa Ontario Canada
| | - Carole Dennie
- 4 Department of Radiology The Ottawa Hospital Ottawa Ontario Canada
| | - Sudhir Nagpal
- 5 Division of Vascular Surgery The Ottawa Hospital Ottawa Ontario Canada
| | | | - Thais Coutinho
- 3 Division of Cardiology University of Ottawa Heart Institute Ottawa Ontario Canada.,6 Division of Cardiac Prevention and Rehabilitation University of Ottawa Heart Institute Ottawa Ontario Canada
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