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Zhu T, Ding Y, Wu X, Li Y, Cheng G, Wang N, Yang Q, Zhang W, Chen X, Liu X. Pentraxin 3 promotes the expression of pro-inflammatory cytokines and the migration of macrophages in myocarditis. BMC Cardiovasc Disord 2025; 25:354. [PMID: 40335910 PMCID: PMC12060373 DOI: 10.1186/s12872-025-04790-w] [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: 11/24/2024] [Accepted: 04/21/2025] [Indexed: 05/09/2025] Open
Abstract
BACKGROUND This study aims to investigate the expression of Pentraxin 3 (PTX3) and Nod-like receptor family pyrin domain-containing 3 (NLRP3) in myocarditis and to elucidate their roles and potential interplay in the pathogenesis of myocarditis. METHODS Immunofluorescence staining was performed on myocardial autopsy specimens from deceased patients with severe myocarditis or severe trauma. H9C2 cardiomyocytes were divided into five groups: Control, Lipopolysaccharide (LPS), LPS + PTX3 overexpression, LPS + small interfering RNA targeting PTX3 (si-PTX3), and LPS + PTX3 overexpression + si-NLRP3. The expression levels of PTX3 and NLRP3 at the RNA level were quantified using quantitative real-time polymerase chain reaction (qPCR), while protein expression was assessed via western blot. The concentrations of interleukin-1β (IL-1β) and IL-18 were determined by enzyme-linked immunosorbent assay (ELISA). Macrophages migration was evaluated using Transwell assays. RESULTS Immunofluorescence staining revealed co-localization and increased expression of PTX3 and NLRP3 in the myocardium of patients with severe myocarditis. In vitro experiments demonstrated that PTX3 enhanced the expression of NLRP3, IL-1β, and IL-18 in LPS-stimulated cardiomyocytes. Furthermore, PTX3 was shown to promote macrophage migration by regulating NLRP3 expression, as assessed by Transwell assays. CONCLUSION Our findings suggest that PTX3-mediated NLRP3 activation contributes to inflammatory responses and promotes macrophage migration in myocarditis. This study provides a foundation for future investigations into PTX3-targeted therapies for myocarditis.
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Affiliation(s)
- Tianyu Zhu
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
| | - Ying Ding
- Department of Nephrology, The Second Medical Center of Chinese PLA General Hospital, National Clinical Research Centre for Geriatric Diseases, Beijing, 100853, P.R. China
| | - Xiaohui Wu
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
| | - Yan Li
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
| | - Guanliang Cheng
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
| | - Ning Wang
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
| | - Quan Yang
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
| | - Wenchao Zhang
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
| | - Xuezhi Chen
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China.
| | - Xiaohui Liu
- Department of Cardiology, Peking University International Hospital, Beijing, 102206, P.R. China
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Das S, Ramanathan G. Assessing the Inhibitory Potential of Pregnenolone Sulfate on Pentraxin 3 in Diabetic Kidney Disease: A Molecular Docking and Simulation Study. J Cell Biochem 2025; 126:e30661. [PMID: 39344977 DOI: 10.1002/jcb.30661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/07/2024] [Accepted: 09/11/2024] [Indexed: 10/01/2024]
Abstract
Diabetic Kidney Disease (DKD), a frequent consequence of diabetes, has substantial implications for both morbidity and mortality rates, prompting the exploration of new metabolic biomarkers due to limitations in current methods like creatinine and albumin measurements. Pentraxin 3 (PTX3) shows promise for assessing renal inflammation in DKD. This study investigates how DKD metabolites could influence PTX3 expression through molecular docking, ADMET profiling, and dynamic simulation. Network and pathway analyses were conducted to explore metabolite interactions with DKD genes and their contributions to DKD pathogenesis. Thirty-three DKD-associated metabolites were screened, using pentoxifylline (PEN) as a reference. The pharmacokinetic properties of these compounds were evaluated through molecular docking and ADMET profiling. Molecular dynamics simulations over 200 ns assessed the stability of PTX3 (apo), the PRE-PTX3 complex, and PEN-PTX3 across multiple parameters. Cytoscape identified 1082 nodes and 1381 edges linking metabolites with DKD genes. KEGG pathway analysis underscored PTX3's role in inflammation. Molecular docking revealed pregnenolone sulfate (PRE) with the highest binding affinity (-6.25 kcal/mol), followed by hydrocortisone (-6.03 kcal/mol) and 2-arachidonoylglycerol (-5.92 kcal/mol), compared to PEN (-5.35 kcal/mol). ADMET profiling selected PRE for dynamic simulation alongside PEN. Analysis of RMSD, RMSF, RG, SASA, H-bond, PCA, FEL, and MM-PBSA indicated stable complex behavior over time. Our findings suggest that increasing PRE levels could be beneficial in managing DKD, potentially through isolating PRE from fungal sources, synthesizing it as dietary supplements, or enhancing endogenous PRE synthesis within the body.
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Affiliation(s)
- Soumik Das
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
| | - Gnanasambandan Ramanathan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India
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Kim S, Hwang AR, Kim SH, Lim JH, Woo CH. Pentraxin 3 deficiency ameliorates streptozotocin-induced pancreatic toxicity via regulating ER stress and β-cell apoptosis. Mol Cells 2025; 48:100168. [PMID: 39657836 PMCID: PMC11742826 DOI: 10.1016/j.mocell.2024.100168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 11/06/2024] [Accepted: 12/04/2024] [Indexed: 12/12/2024] Open
Abstract
The long pentraxin 3 (PTX3), a marker of inflammation, has been associated with cardiovascular disease, obesity, and metabolic syndrome. Recently, elevated serum PTX3 levels have been linked to type 2 diabetes in obese patients with nonalcoholic fatty liver disease. Diabetes mellitus is a metabolic syndrome characterized by hyperglycemia resulting from insufficient insulin secretion or action. However, the precise role of PTX3 in hyperglycemia remains unclear. This study aimed to investigate the physiological roles of PTX3 in vivo. The deformation of pancreatic islets was mitigated in PTX3-deficient mice treated with streptozotocin (STZ) compared to control C57BL/6J mice. In addition, PTX3 deficiency prevented STZ-induced unfolded protein responses and pancreatic β-cell death. Immunoblotting data revealed significant inhibition of inositol-requiring protein1α and C/EBP homologous protein (CHOP) protein expression in PTX3 KO mice administered tunicamycin which is a chemical endoplasmic reticulum stress inducer. Similarly, tunicamycin-induced Grp78, Grp94, ATF6, and CHOP mRNA levels were reduced in PTX3 KO mice. Moreover, recombinant PTX3-induced CHOP expression and β-cell apoptosis in primary mouse islets. These findings suggest that PTX3 plays a critical role in STZ-induced deformation of pancreatic islets via regulating endoplasmic reticulum stress and β-cell apoptosis.
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Affiliation(s)
- Suji Kim
- Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of Korea; Division of Cardiovascular Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, 197 Osongsaengmyeng2-ro, Osong-eub, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do 28159, Republic of Korea
| | - Ae-Rang Hwang
- Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of Korea
| | - Sun-Hee Kim
- Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of Korea
| | - Jae Hyang Lim
- Department of Microbiology, Ewha Womans University College of Medicine, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul 07804, Republic of Korea.
| | - Chang-Hoon Woo
- Department of Pharmacology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of Korea; Senotherapy-based Metabolic Disease Control Research Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of Korea.
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4
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Anderson MR, Kim JS, Podolanczuk A, Ding J, Al‐Naamani N, Allison M, Christie J, Diamond J. Nonlinear associations between computed tomography-measures of adiposity and long pentraxin-3 in the Multi-Ethnic Study of Atherosclerosis. Obes Sci Pract 2024; 10:e708. [PMID: 38263991 PMCID: PMC10804353 DOI: 10.1002/osp4.708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 08/03/2023] [Accepted: 08/25/2023] [Indexed: 01/25/2024] Open
Abstract
Objective Long pentraxin-3 (PTX-3) is an acute phase protein associated with cardiovascular disease, lung injury, and mortality. We evaluated the association between computed tomography (CT)-measurements of adipose tissue and plasma levels of PTX-3. Methods We performed a cross-sectional analysis of community-dwelling adults enrolled in the multi-center Multiethnic Study of Atherosclerosis who underwent cardiac or abdominal CT and had available PTX-3 measurements. Results There was a U-shaped association between pericardial adipose tissue volume (PAT), abdominal visceral adipose tissue area (VAT), hepatic attenuation, and PTX-3 levels, with extremes of adiposity associated with greater PTX-3 levels. Using multivariable-adjusted piecewise regression models, among participants with low PAT, every 1% increase in PAT volume was associated with a 13.8% decrease in PTX-3 (95% confidence interval [CI] -21.6 to -6.0); among participants with high PAT, every 1% increase in PAT volume was associated with a 6.0% increase in PTX-3 (95% CI -0.4 to 12.5). Results were similar for abdominal VAT and hepatic attenuation. Conclusions In a cohort of community-dwelling adults, we demonstrated a "U-shaped" association between pericardial, abdominal visceral, and hepatic adiposity with PTX3 levels, suggesting that extreme adiposity is associated with greater circulating levels of PTX3. Further work is required to identify the mechanisms linking adiposity and PTX-3.
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Affiliation(s)
| | - John S. Kim
- Department of MedicineUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Anna Podolanczuk
- Department of MedicineWeill Cornell Medical CollegeNew YorkNew YorkUSA
| | - Jingzhong Ding
- Department of Epidemiology and PreventionWake Forest UniversityWinston‐SalemNorth CarolinaUSA
- Department of Gerontology and Geriatric ScienceWake Forest UniversityWinston‐SalemNorth CarolinaUSA
| | - Nadine Al‐Naamani
- Department of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Matthew Allison
- Department of Preventive MedicineUniversity of California San DiegoSan DiegoCaliforniaUSA
| | - Jason Christie
- Department of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Joshua Diamond
- Department of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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Ye X, Wang Z, Lei W, Shen M, Tang J, Xu X, Yang Y, Zhang H. Pentraxin 3: A promising therapeutic target for cardiovascular diseases. Ageing Res Rev 2024; 93:102163. [PMID: 38092307 DOI: 10.1016/j.arr.2023.102163] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 11/23/2023] [Accepted: 12/07/2023] [Indexed: 12/18/2023]
Abstract
Cardiovascular disease (CVD) is the primary global cause of death, and inflammation is a crucial factor in the development of CVDs. The acute phase inflammatory protein pentraxin 3 (PTX3) is a biomarker reflecting the immune response. Recent research indicates that PTX3 plays a vital role in CVDs and has been investigated as a possible biomarker for CVD in clinical trials. PTX3 is implicated in the progression of CVDs through mechanisms such as exacerbating vascular endothelial dysfunction, affecting angiogenesis, and regulating inflammation and oxidative stress. This review summarized the structure and function of PTX3, focusing on its multifaceted effects on CVDs, such as atherosclerosis, myocardial infarction, and hypertension. This may help in explaining the varying PTX3 functions and usage, as well as in utilizing target organs to manage diseases. Moreover, elucidating the opposite role of PTX3 in the cardiovascular system will demonstrate the therapeutic and predictive potential in human diseases.
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Affiliation(s)
- Xingyan Ye
- Department of Cardiology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, China; Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, Xi'an, China
| | - Zheng Wang
- Department of Cardiothoracic Surgery, Central Theater Command General Hospital of Chinese People's Liberation Army, 627 Wuluo Road, Wuhan, China
| | - Wangrui Lei
- Department of Cardiology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, China
| | - Mingzhi Shen
- Department of General Medicine, Hainan Hospital of Chinese People's Liberation Army (PLA) General Hospital, 80 Jianglin Road, Hainan, China
| | - Jiayou Tang
- Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, China
| | - Xuezeng Xu
- Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, China
| | - Yang Yang
- Department of Cardiology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, China; Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, Xi'an, China.
| | - Huan Zhang
- Department of Cardiology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, 10 Fengcheng Three Road, Xi'an, China; Xi'an Key Laboratory of Innovative Drug Research for Heart Failure, Faculty of Life Sciences and Medicine, Northwest University, 229 Taibai North Road, Xi'an, China.
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Li Y, Zhang S, Liu J, Zhang Y, Zhang N, Cheng Q, Zhang H, Wu X. The pentraxin family in autoimmune disease. Clin Chim Acta 2023; 551:117592. [PMID: 37832905 DOI: 10.1016/j.cca.2023.117592] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/08/2023] [Accepted: 10/10/2023] [Indexed: 10/15/2023]
Abstract
The pentraxins represent a family of multifunctional proteins composed of long and short pentamers. The latter includes serum amyloid P component (SAP) and C-reactive protein (CRP) whereas the former includes neuronal PTX1 and PTX2 (NPTX1 and NPTX2, respectively), PTX3 and PTX4. These serve as a bridge between adaptive immunity and innate immunity and a link between inflammation and immunity. Similarities and differences between long and short pentamers are examined and their roles in autoimmune disease are discussed. Increased CRP and PTX3 could indicate the activity of rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases. Mechanistically, CRP and PTX3 may predict target organ injury, regulate bone metabolic immunity and maintain homeostasis as well as participate in vascular endothelial remodeling. Interestingly, PTX3 is pleiotropic, being involved in inflammation and tissue repair. Given the therapeutic potential of PTX3 and CRP, targeting these factors to exert a beneficial effect is the focus of research efforts. Unfortunately, studies on NPTX1, NPTX2, PTX4 and SAP are scarce and more research is clearly needed to elaborate their potential roles in autoimmune disease.
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Affiliation(s)
- Yongzhen Li
- Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China
| | - Shouzan Zhang
- Department of Neurosurgery, Peking University Third Hospital, Beijing, PR China
| | - Jingqi Liu
- Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China
| | - Yudi Zhang
- Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China
| | - Nan Zhang
- College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Quan Cheng
- Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, PR China.
| | - Hao Zhang
- Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.
| | - Xiaochuan Wu
- Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
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Bousquet E, Chenevier-Gobeaux C, Jaworski T, Torres-Villaros H, Zola M, Mantel I, Kowalczuk L, Matet A, Daruich A, Zhao M, Yzer S, Behar-Cohen F. High Levels of C-Reactive Protein with Low Levels of Pentraxin 3 as Biomarkers for Central Serous Chorioretinopathy. OPHTHALMOLOGY SCIENCE 2023; 3:100278. [PMID: 36950301 PMCID: PMC10025279 DOI: 10.1016/j.xops.2023.100278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 01/26/2023] [Accepted: 01/27/2023] [Indexed: 02/05/2023]
Abstract
Purpose To investigate the association between the 2 acute phase proteins, C-reactive protein (CRP) and pentraxin 3 (PTX3) with central serous chorioretinopathy (CSCR), as PTX3 is a glucocorticoid-induced protein. Design Cross-sectional multicenter study. Participants Patients with CSCR compared with age- and sex-matched healthy participants. Methods Patients with CSCR from 3 centers in Europe were included in the study. The clinical form of CSCR was recorded. Blood samples from patients with CSCR and healthy participants were sampled, and high-sensitivity CRP and PTX3 levels were measured in the serum. Main Outcome Measures C-reactive protein and PTX3 serum level comparison between patients with CSCR with age- and sex-matched healthy participants. Results Although CRP levels were higher in patients with CSCR (n = 216) than in age- and sex-matched controls (n = 130) (2.2 ± 3.2 mg/l vs. 1.5 mg/l ± 1.4, respectively, P = 0.037), PTX3 levels were lower in patients with CSCR (10.5 ± 19.9 pg/ml vs. 87.4 ± 73.2 pg/ml, respectively, P < 0.001). There was no significant difference in CRP or PTX3 levels between patients with acute/recurrent and chronic CSCR. Conclusions In patients with CSCR, high CRP and low PTX3 levels suggest a form of low-grade systemic inflammation together with a lack of glucocorticoid pathway activation, raising new hypotheses on the pathophysiology of CSCR. Financial Disclosures The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Affiliation(s)
- Elodie Bousquet
- Department of Ophthalmology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
- Centre de Recherche des Cordeliers, INSERM, University of Paris Cité, Physiopathology of ocular diseases: Therapeutic innovations, Paris, France
| | - Camille Chenevier-Gobeaux
- Service de diagnostic biologique automatisé, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
| | - Thara Jaworski
- Centre de Recherche des Cordeliers, INSERM, University of Paris Cité, Physiopathology of ocular diseases: Therapeutic innovations, Paris, France
| | - Héloïse Torres-Villaros
- Department of Ophthalmology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
| | - Marta Zola
- Department of Ophthalmology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
- Centre de Recherche des Cordeliers, INSERM, University of Paris Cité, Physiopathology of ocular diseases: Therapeutic innovations, Paris, France
| | - Irmela Mantel
- Department of Ophthalmology, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Switzerland
| | - Laura Kowalczuk
- Department of Ophthalmology, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Switzerland
| | - Alexandre Matet
- Department of Ophthalmology, Institut Curie, University of Paris Cité, Paris, France
| | - Alejandra Daruich
- Centre de Recherche des Cordeliers, INSERM, University of Paris Cité, Physiopathology of ocular diseases: Therapeutic innovations, Paris, France
- Department of Ophthalmology, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
| | - Min Zhao
- Centre de Recherche des Cordeliers, INSERM, University of Paris Cité, Physiopathology of ocular diseases: Therapeutic innovations, Paris, France
| | - Suzanne Yzer
- Department of Ophthalmology, Rotterdam Eye Hospital, Rotterdam, the Netherlands
| | - Francine Behar-Cohen
- Department of Ophthalmology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris Cité, Paris, France
- Centre de Recherche des Cordeliers, INSERM, University of Paris Cité, Physiopathology of ocular diseases: Therapeutic innovations, Paris, France
- Correspondence: Francine Behar-Cohen, MD, PhD, centre de recherche des cordeliers, 15 rue de l’école de médecine, 75006 Paris, France.
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Ohnishi N, Shiga Y, Tashiro K, Kawahira Y, Shibata Y, Inoue H, Morii J, Nishikawa H, Kato Y, Kuwano T, Sugihara M, Miura SI. Association between major adverse cardiovascular events and pentraxin-3 in patients who have undergone coronary computed tomography angiography: from the FU-CCTA registry. Heart Vessels 2023; 38:309-317. [PMID: 36169707 DOI: 10.1007/s00380-022-02171-3] [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: 03/22/2022] [Accepted: 08/31/2022] [Indexed: 02/07/2023]
Abstract
Chronic vasculitis is considered to be associated with future cardiovascular events. Here, we present major cardiovascular events (MACEs) in patients who underwent coronary computed tomography angiography (CCTA) for screening for coronary artery disease (CAD), and the association between MACEs and the inflammation marker pentraxin (PTX)-3 or highly sensitive C-reactive protein (hsCRP). The patients who underwent CCTA for the purpose of screening for CAD at Fukuoka University Hospital (FU-CCTA registry), 456 patients with suspected CAD or at least one cardiovascular risk factor were followed for up to 5 years. The levels of PTX-3 and hsCRP in blood were measured at the time of CCTA, and the patients were divided into two groups according to the presence (MACEs group) or absence (non-MACEs group) of MACEs. There were no differences in PTX-3 or hsCRP between the MACEs (-) and MACEs ( +) groups in all patients. A multivariate analysis related to the presence or absence of MACEs by logistic regression analysis of inflammation factors (PTX-3 and hsCRP) in addition to conventional risk factors as independent variables was performed. PTX-3 was a predictor of MACEs in males, whereas smoking, but not PTX-3, was a predictor of MACEs in females. PTX-3 could be a predictor of MACEs in males, but not females.
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Affiliation(s)
- Natsuki Ohnishi
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.,Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan
| | - Yuhei Shiga
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Kohei Tashiro
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Yuto Kawahira
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Yuuka Shibata
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Hiroko Inoue
- Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan
| | - Joji Morii
- Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan
| | - Hiroaki Nishikawa
- Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan
| | - Yuta Kato
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Takashi Kuwano
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Makoto Sugihara
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan
| | - Shin-Ichiro Miura
- Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. .,Department of Cardiology, Fukuoka University Nishijin Hospital, Fukuoka, Japan.
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9
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Soysal Gündüz Ö, Armağan Alptürker K, Güler Şen M, Can F, Erdal S, Ulman C, Pırıldar T. The Relationship of Carotid Intima-Media Thickness with Cell Adhesion
Molecules and Pentraxin-3 in Patients with Psoriatic Arthritis. AKTUEL RHEUMATOL 2023. [DOI: 10.1055/a-1942-6311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Abstract
Aim Cardiovascular morbidity is increased in patients with psoriatic
arthritis (PsA) compared to the general population. Several recent studies have
indicated that pentraxin 3 (PTX-3) and cell adhesion molecules (CAMs) might be
independent biomarkers of subclinical atherosclerosis. In this study, we aimed
to determine the relationship of CAMs and PTX-3 with carotid intima media
thickness (CIMT) in patients with PsA and to compare CIMT and serum levels of
these biomarkers in patients with healthy controls (HCs).
Method PsA patients fulfilling the CASPAR (Classification criteria for
Psoriatic Arthritis) criteria without traditional cardiovascular (CV)
comorbidity and HCs without autoimmune and/or CV disease were included
in this cross-sectional study. Carotid artery Doppler ultrasound examinations
were conducted by a single radiologist blinded to the participants’
clinical characteristics. Serum vascular adhesion molecule 1 (VCAM-1),
intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PTX-3 concentrations
were analized.
Results 43 PsA patients (27 females, mean age 42.49±11.70 years,
and a mean disease duration of 9.37±7.96 years) and 37 HCs (28 females,
mean age 42.16±11.38 years) were included. In regression analyses, age
and PTX-3 were found to be the best predictors of CIMT in patients with PsA.
CIMT was significantly higher in PsA patients compared with HCs
(0.63±0.18 vs. 0.49±0.10 mm, p<0.01). In te PsA
group, serum levels of PTX-3, ICAM-1, and VCAM-1 were also significantly higher
than HCs. CIMT correlated positively with age, disease duration, PTX-3, ICAM-1,
and VCAM-1 (p<0.05).
Conclusion In our study, age and serum level of PTX-3 were found to be the
predictors of CIMT in patients with PsA without CV comorbidity. This outcome
highlights the importance of monitoring CIMT and serum level of PTX-3 as CV risk
factors in PsA patients.
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Affiliation(s)
- Özgü Soysal Gündüz
- Faculty of Medicine, Department of Internal Medicine, Division of
Rheumatology, Manisa Celal Bayar University, Manisa, Turkey
| | - Kezban Armağan Alptürker
- Faculty of Medicine, Department of Physical Medicine and
Rehabilitation, Division of Rheumatology, Manisa Celal Bayar University, Manisa,
Turkey
| | - Menice Güler Şen
- Faculty of Medicine, Department of Internal Medicine, Division of
Rheumatology, Manisa Celal Bayar University, Manisa, Turkey
| | - Fatma Can
- Faculty of Medicine, Department of Radiology, Manisa Celal Bayar
University, Manisa, Turkey
| | - Serkan Erdal
- Faculty of Medicine, Department of Medical Biochemistry, Manisa Celal
Bayar University, Manisa, Turkey
| | - Cevval Ulman
- Faculty of Medicine, Department of Medical Biochemistry, Manisa Celal
Bayar University, Manisa, Turkey
| | - Timur Pırıldar
- Faculty of Medicine, Department of Internal Medicine, Division of
Rheumatology, Manisa Celal Bayar University, Manisa, Turkey
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10
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Bordeianu G, Mitu I, Stanescu RS, Ciobanu CP, Petrescu-Danila E, Marculescu AD, Dimitriu DC. Circulating Biomarkers for Laboratory Diagnostics of Atherosclerosis-Literature Review. Diagnostics (Basel) 2022; 12:diagnostics12123141. [PMID: 36553147 PMCID: PMC9777004 DOI: 10.3390/diagnostics12123141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/05/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
Atherosclerosis is still considered a disease burden with long-term damaging processes towards the cardiovascular system. Evaluation of atherosclerotic stages requires the use of independent markers such as those already considered traditional, that remain the main therapeutic target for patients with atherosclerosis, together with emerging biomarkers. The challenge is finding models of predictive markers that are particularly tailored to detect and evaluate the evolution of incipient vascular lesions. Important advances have been made in this field, resulting in a more comprehensible and stronger linkage between the lipidic profile and the continuous inflammatory process. In this paper, we analysed the most recent data from the literature studying the molecular mechanisms of biomarkers and their involvement in the cascade of events that occur in the pathophysiology of atherosclerosis.
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Affiliation(s)
| | - Ivona Mitu
- Correspondence: (I.M.); (R.S.S.); Tel.: +40-75206-1747 (I.M.)
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11
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Zhang H, Wang R, Wang Z, Wu W, Zhang N, Zhang L, Hu J, Luo P, Zhang J, Liu Z, Feng S, Peng Y, Liu Z, Cheng Q. Molecular insight into pentraxin-3: Update advances in innate immunity, inflammation, tissue remodeling, diseases, and drug role. Biomed Pharmacother 2022; 156:113783. [PMID: 36240615 DOI: 10.1016/j.biopha.2022.113783] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 09/28/2022] [Accepted: 09/28/2022] [Indexed: 11/20/2022] Open
Abstract
Pentraxin-3 (PTX3) is the prototype of the long pentraxin subfamily, an acute-phase protein consisting of a C-terminal pentraxin domain and a unique N-terminal domain. PTX3 was initially isolated from human umbilical vein endothelial cells and human FS-4 fibroblasts. It was subsequently found to be also produced by synoviocytes, chondrocytes, osteoblasts, smooth muscle cells, myeloid dendritic cells, epithelial cells, and tumor cells. Various modulatory factors, such as miRNAs, cytokines, drugs, and hypoxic conditions, could regulate the expression level of PTX3. PTX3 is essential in regulating innate immunity, inflammation, angiogenesis, and tissue remodeling. Besides, PTX3 may play dual (pro-tumor and anti-tumor) roles in oncogenesis. PTX3 is involved in the occurrence and development of many non-cancerous diseases, including COVID-19, and might be a potential biomarker indicating the prognosis, activity,and severity of diseases. In this review, we summarize and discuss the potential roles of PTX3 in the oncogenesis and pathogenesis of non-cancerous diseases and potential targeted therapies based on PTX3.
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Affiliation(s)
- Hao Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China; Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, China
| | - Ruixuan Wang
- Department of Oncology, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Zeyu Wang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Wantao Wu
- Department of Oncology, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Nan Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; One-third Lab, College of Bioinformatics Science and Technology, Harbin Medical University, China
| | - Longbo Zhang
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; Department of Neurosurgery, and Department of Cellular & Molecular Physiology,Yale University School of Medicine, USA; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Jason Hu
- Department of Neonatology, Yale University School of Medicine, USA
| | - Peng Luo
- Department of Oncology, Zhujiang Hospital, Southern Medical University, China
| | - Jian Zhang
- Department of Oncology, Zhujiang Hospital, Southern Medical University, China
| | - Zaoqu Liu
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, China
| | - Songshan Feng
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Yun Peng
- Department of Geriatrics, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
| | - Zhengzheng Liu
- Department of Oncology, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China.
| | - Quan Cheng
- Department of Neurosurgery, Xiangya Hospital, Central South University, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China.
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12
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Dincer E, Topçuoğlu S, Arman D, Kaya A, Yavuz T, Karatekin G. Inflammation Markers in Infants of Mothers with Gestational Diabetes. Fetal Pediatr Pathol 2022; 41:616-626. [PMID: 34280066 DOI: 10.1080/15513815.2021.1945715] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
AimPentraxin-3, high sensitive CRP (HsCRP) and adropin were investigated in cord blood of infants of mothers with gestational diabetes mellitus (IDM) to evaluate the exposure of fetus to inflammation and whether there is any correlation with clinical findings.MethodsForty IDM and forty three infants whose mother did not have diabetes were included in this prospective study. Adropin, pentraxin-3 and HsCRP levels were measured in the cord blood samples. Echocardiographic measurements were performed in the first three days of life.ResultsAdropin and pentraxine-3 levels were significantly lower and HsCRP levels were significantly higher in IDM group. Echocardiographic measurements of myocardial hypertrophy were negatively correlated with adropin.ConclusionAlterations in these markers in IDM supports the hypothesis of in utero fetal exposure to inflammation caused by gestational diabetes mellitus. Potentially, cord blood adropin might be used as a predictor for complications of diabetes.
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Affiliation(s)
- Emre Dincer
- Neonatal Intensive Care Unit, Health Sciences University, Istanbul Zeynep Kamil Maternity and Children's Hospital Research and Training Hospital, Üsküdar Istanbul, Turkey
| | - Sevilay Topçuoğlu
- Neonatal Intensive Care Unit, Health Sciences University, Istanbul Zeynep Kamil Maternity and Children's Hospital Research and Training Hospital, Üsküdar Istanbul, Turkey
| | - Didem Arman
- Neonatal Intensive Care Unit, Health Sciences University, Istanbul Zeynep Kamil Maternity and Children's Hospital Research and Training Hospital, Üsküdar Istanbul, Turkey
| | - Ayşem Kaya
- Haseki Cardiology Institute, İstanbul University, Istanbul, Turkey
| | - Taner Yavuz
- Okan University Medical Faculty, Department of Pediatrics, Pediatric Cardiology, Okan University, Istanbul, Turkey
| | - Güner Karatekin
- Neonatal Intensive Care Unit, Health Sciences University, Istanbul Zeynep Kamil Maternity and Children's Hospital Research and Training Hospital, Üsküdar Istanbul, Turkey
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13
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Brady EM, Gulsin GS, Mirkes EM, Parke K, Kanagala P, Ng LL, Graham‐Brown MPM, Athithan L, Henson J, Redman E, Yang J, Zhao L, Argyridou S, Gray LJ, Yates T, Davies MJ, McCann GP. Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial. Diabet Med 2022; 39:e14884. [PMID: 35587779 PMCID: PMC9543965 DOI: 10.1111/dme.14884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 05/08/2022] [Indexed: 12/15/2022]
Abstract
AIMS To investigate the relationship between fibro-inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D. METHODS Data were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12-week intervention either: (1) exercise training, (2) a low-energy (∼810 kcal/day) meal-replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro-inflammatory biomarkers in cases versus controls and pre- and post-intervention in T2D. RESULTS At baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre- post-analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro-inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training. CONCLUSIONS Fibro-inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle-aged adults with T2D. The MRP improved the fibro-inflammatory profile of people with T2D towards a more healthy status. Long-term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.
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Affiliation(s)
- Emer M. Brady
- Department of Cardiovascular SciencesUniversity of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research CentreLeicesterUK
| | - Gaurav S. Gulsin
- Department of Cardiovascular SciencesUniversity of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research CentreLeicesterUK
| | - Evgeny M. Mirkes
- School of Mathematics and Actuarial ScienceUniversity of LeicesterLeicesterUK
| | - Kelly Parke
- Department of Cardiovascular SciencesUniversity of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research CentreLeicesterUK
| | - Prathap Kanagala
- University of LiverpoolLiverpool Centre for Cardiovascular ScienceLiverpoolUK
| | - Leong L. Ng
- Department of Cardiovascular SciencesUniversity of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research CentreLeicesterUK
| | - Matthew P. M. Graham‐Brown
- Department of Cardiovascular SciencesUniversity of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research CentreLeicesterUK
| | - Lavanya Athithan
- Department of Cardiovascular SciencesUniversity of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research CentreLeicesterUK
| | - Joseph Henson
- Diabetes Research CentreNIHR Leicester Biomedical Research CentreLeicesterUK
| | - Emma Redman
- Diabetes Research CentreNIHR Leicester Biomedical Research CentreLeicesterUK
- University Hospitals of Leicester NHS TrustLeicesterUK
| | - Jang Yang
- Cardiovascular & Fibrosis Translational ResearchBristolNew JerseyUSA
| | - Lei Zhao
- Cardiovascular & Fibrosis Translational ResearchBristolNew JerseyUSA
| | - Stavroula Argyridou
- Diabetes Research CentreNIHR Leicester Biomedical Research CentreLeicesterUK
| | - Laura J. Gray
- Department of Health SciencesUniversity of LeicesterLeicesterUK
| | - Thomas Yates
- Diabetes Research CentreNIHR Leicester Biomedical Research CentreLeicesterUK
| | - Melanie J. Davies
- Diabetes Research CentreNIHR Leicester Biomedical Research CentreLeicesterUK
- University Hospitals of Leicester NHS TrustLeicesterUK
| | - Gerry P. McCann
- Department of Cardiovascular SciencesUniversity of Leicester and the National Institute for Health Research (NIHR) Leicester Biomedical Research CentreLeicesterUK
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14
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Upadhya R, Madhu LN, Rao S, Shetty AK. Proficiency of Extracellular Vesicles From hiPSC-Derived Neural Stem Cells in Modulating Proinflammatory Human Microglia: Role of Pentraxin-3 and miRNA-21-5p. Front Mol Neurosci 2022; 15:845542. [PMID: 35656007 PMCID: PMC9152457 DOI: 10.3389/fnmol.2022.845542] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 03/22/2022] [Indexed: 12/05/2022] Open
Abstract
Extracellular vesicles (EVs) shed by human-induced pluripotent stem cell (hiPSC)-derived neural stem cells (hNSC-EVs) have shown potent antiinflammatory properties in a mouse macrophage assay and a mouse model of acute neuroinflammation. They can also quickly permeate the entire brain after intranasal administration, making them attractive as an autologous or allogeneic off-the-shelf product for treating neurodegenerative diseases. However, their ability to modulate activated human microglia and specific proteins and miRNAs mediating antiinflammatory effects of hNSC-EVs are unknown. We investigated the proficiency of hNSC-EVs to modulate activated human microglia and probed the role of the protein pentraxin 3 (PTX3) and the miRNA miR-21-5p within hNSC-EVs in mediating the antiinflammatory effects. Mature microglia generated from hiPSCs (iMicroglia) expressed multiple microglia-specific markers. They responded to lipopolysaccharide (LPS) or interferon-gamma challenge by upregulating tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) mRNA expression and protein release. iMicroglia also exhibited proficiency to phagocytose amyloid-beta (Aβ). The addition of hNSC-EVs decreased TNF-α and IL-1β mRNA expression and the release of TNF-α and IL-1β by LPS-stimulated iMicroglia (proinflammatory human Microglia). However, the antiinflammatory activity of hNSC-EVs on LPS-stimulated microglia was considerably diminished when the PTX3 or miR-21-5p concentration was reduced in EVs. The results demonstrate that hNSC-EVs are proficient for modulating the proinflammatory human microglia into non-inflammatory phenotypes, implying their utility to treat neuroinflammation in neurodegenerative diseases. Furthermore, the role of PTX3 and miR-21-5p in the antiinflammatory activity of hNSC-EVs provides a new avenue for improving the antiinflammatory effects of hNSC-EVs through PTX3 and/or miR-21-5p overexpression.
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15
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Phetsouphanh C, Darley DR, Wilson DB, Howe A, Munier CML, Patel SK, Juno JA, Burrell LM, Kent SJ, Dore GJ, Kelleher AD, Matthews GV. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol 2022; 23:210-216. [PMID: 35027728 DOI: 10.1038/s41590-021-01113-x] [Citation(s) in RCA: 593] [Impact Index Per Article: 197.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 12/01/2021] [Indexed: 02/07/2023]
Abstract
A proportion of patients surviving acute coronavirus disease 2019 (COVID-19) infection develop post-acute COVID syndrome (long COVID (LC)) lasting longer than 12 weeks. Here, we studied individuals with LC compared to age- and gender-matched recovered individuals without LC, unexposed donors and individuals infected with other coronaviruses. Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection. Using a log-linear classification model, we defined an optimal set of analytes that had the strongest association with LC among the 28 analytes measured. Combinations of the inflammatory mediators IFN-β, PTX3, IFN-γ, IFN-λ2/3 and IL-6 associated with LC with 78.5-81.6% accuracy. This work defines immunological parameters associated with LC and suggests future opportunities for prevention and treatment.
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Affiliation(s)
| | - David R Darley
- St Vincent's Hospital, Darlinghurst, New South Wales, Australia
| | - Daniel B Wilson
- Department of Mathematics and Statistics, Boston University, Boston, MA, USA
| | - Annett Howe
- The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
| | - C Mee Ling Munier
- The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
| | - Sheila K Patel
- Department of Medicine, Austin Health, University of Melbourne, Melbourne, Victoria, Australia
| | - Jennifer A Juno
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia
| | - Louise M Burrell
- Department of Medicine, Austin Health, University of Melbourne, Melbourne, Victoria, Australia
| | - Stephen J Kent
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia
- Melbourne Sexual Health Centre, Infectious Diseases Department, Alfred Health, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Gregory J Dore
- The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
- St Vincent's Hospital, Darlinghurst, New South Wales, Australia
| | - Anthony D Kelleher
- The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
- St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
| | - Gail V Matthews
- The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
- St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
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16
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Alieva AM, Teplova NV, Batov MA, Voronkova KV, Valiev RK, Shnakhova LM, Pinchuk TV, Rakhaev AM, Kalova MR, Nikitin IG. Pentraxin-3 – a promising biological marker in heart failure: literature review. CONSILIUM MEDICUM 2022. [DOI: 10.26442/20751753.2022.1.201382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
According to many studies, inflammation plays a very significant role in the pathogenesis of heart failure. Many studies have demonstrated an increase in circulating levels of inflammatory markers and cytokines such as C-reactive protein, tumor necrosis factor-a (TNF-a), and interleukins. C-reactive protein is produced in the liver in response to stimulation by various cytokines, mainly interleukin-6, and is a member of the pentraxin superfamily. Pentraxin-3, which is a long pentraxin, has a C-terminal domain of pentraxin similar to the classic short pentraxins, but differs from them in the presence of an unrelated long N-terminal domain. Various cell types can produce pentraxin-3 when exposed to primary inflammatory signals such as interleukin-1, tumor necrosis (TNF-a), oxidized low density lipoprotein, and microbial fragments (eg, lipopolysaccharide, lipoarabinomannans). Data in experimental animal models have demonstrated that pentraxin-3 can play cardioprotective and atheroprotective roles through its influence on the inflammatory process. Pentraxin-3 has been studied in several clinical protocols as a potential biomarker for cardiovascular disease.
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17
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Severity Biomarkers in Puumala Hantavirus Infection. Viruses 2021; 14:v14010045. [PMID: 35062248 PMCID: PMC8778356 DOI: 10.3390/v14010045] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 12/16/2021] [Accepted: 12/23/2021] [Indexed: 12/12/2022] Open
Abstract
Annually, over 10,000 cases of hemorrhagic fever with renal syndrome (HFRS) are diagnosed in Europe. Puumala hantavirus (PUUV) causes most of the European HFRS cases. PUUV causes usually a relatively mild disease, which is rarely fatal. However, the severity of the infection varies greatly, and factors affecting the severity are mostly unrevealed. Host genes are known to have an effect. The typical clinical features in PUUV infection include acute kidney injury, thrombocytopenia, and increased vascular permeability. The primary target of hantavirus is the endothelium of the vessels of different organs. Although PUUV does not cause direct cytopathology of the endothelial cells, remarkable changes in both the barrier function of the endothelium and the function of the infected endothelial cells occur. Host immune or inflammatory mechanisms are probably important in the development of the capillary leakage. Several immunoinflammatory biomarkers have been studied in the context of assessing the severity of HFRS caused by PUUV. Most of them are not used in clinical practice, but the increasing knowledge about the biomarkers has elucidated the pathogenesis of PUUV infection.
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18
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Zhao X, Song L, Wang Y, Li J, Zhou J, Chen R, Liu C, Zhou P, Sheng Z, Chen Y, Zhao H, Yan H. Proprotein Convertase Subtilisin/Kexin Type 9 and Systemic Inflammatory Biomarker Pentraxin 3 for Risk Stratification Among STEMI Patients Undergoing Primary PCI. J Inflamm Res 2021; 14:5319-5335. [PMID: 34703271 PMCID: PMC8524062 DOI: 10.2147/jir.s334246] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 10/07/2021] [Indexed: 12/12/2022] Open
Abstract
Background and Aim The aim of prospective study was to determine the prognostic value of combined measures of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and pentraxin 3 (PTX3) according to the culprit-plaque morphology (plaque rupture versus plaque erosion) in relation to the in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention. Methods A total of 434 patients with STEMI aged ≥18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. Finally, 235 patients who meet the inclusion criteria were enrolled and the cohort was divided into 3 groups according to PCSK9 and PTX3 levels: group A: PCSK9 < median and Pentraxin 3 (N = 72/30.6%); group B: PCSK9 ≥ median or Pentraxin 3≥ median (N = 91/38.7%); group C: PCSK9 ≥ median and Pentraxin 3≥ median (N = 72/30.6%). MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischemic stroke, revascularization and heart failure. Outcomes During a median follow-up of 2.01 years, 50 patients has occurred MACE. Two-year MACE was higher in group C (23/31.9%) than in group B (16/17.6%) and group A (11/15.3%) (p = 0.028). There was a correlation between PCSK9 and PTX3 (r = 0.302, p < 0.003). In multivariable analysis adjusted for age, gender, risk factors, and serum indexes, being in group C remained independently associated with an increased risk of MACE (hazard ratio [HR]: 2.90; p = 0.010), and group B tended to have higher MACE (HR: 1.76; p = 0.172) compared with group A. Among patients with plaque erosion by OCT, group C was independently associated with an increased risk of MACE (HR: 9.04; p = 0.048) after fully adjustment. However, the significant association was absence among patients with plaque rupture. Conclusion and Relevance This study demonstrated the usefulness of combined measures of PCSK9 and PTX3 to enhance risk stratification in patients with STEMI especially among patients with plaque erosion. Patients with elevation of both PCSK9 and PTX3 had a markedly increased risk of MACE.
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Affiliation(s)
- Xiaoxiao Zhao
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Li Song
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Ying Wang
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Jiannan Li
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Jinying Zhou
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Runzhen Chen
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Chen Liu
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Peng Zhou
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Zhaoxue Sheng
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Yi Chen
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Hanjun Zhao
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People's Republic of China
| | - Hongbing Yan
- Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People's Republic of China
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19
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Poloczek J, Tarnawska M, Chełmecka E, Łaszczyca P, Gumprecht J, Stygar D. High Fat, High Sugar Diet and DJOS Bariatric Surgery Influence Plasma Levels of Fetuin-B, Growth Differentiation Factor-15, and Pentraxin 3 in Diet-Induced Obese Sprague-Dawley Rats. Nutrients 2021; 13:nu13103632. [PMID: 34684637 PMCID: PMC8539134 DOI: 10.3390/nu13103632] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 01/14/2023] Open
Abstract
The liver plays a central role in glucose and fatty acid metabolism and acts as an endocrine organ that secretes hepatokines with diverse systemic effects. The study aimed to examine the influence of duodenojejunal omega switch (DJOS) bariatric surgery in combination with different diets on glucose administration parameters and hepatokines levels. After 8 weeks on high fat, high sugar diet (HFS) or control diets (CD), Sprague-Dawley rats underwent DJOS or SHAM (control) surgery. For the next 8 weeks after the surgery, half of DJOS and SHAM-operated animals were kept on the same diet as before, and half had a diet change. The oral glucose tolerance test (OGTT) was performed three times: 8 weeks before and 4 and 8 weeks after surgery. Fetuin-B, growth differentiation factor-15 (GDF-15), pentraxin 3 (PTX3) plasma levels were analyzed. DJOS surgery had a beneficial effect on oral glucose tolerance test (OGTT) results and the area under the curve (AUCOGTT). The OGTT results depended on the time elapsed after the surgery, the type of diet used, the surgery performed, and the interaction between these factors. DJOS bariatric surgery reduced fetuin-B and GDF15 plasma levels. Interaction between the type of surgery performed and diet used influenced the fetuin-B and PTX-3 plasma levels. A dietary regime is essential to achieve therapeutic and clinical goals after bariatric surgery.
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Affiliation(s)
- Jakub Poloczek
- Department of Rehabilitation, 3rd Specialist Hospital in Rybnik, Energetyków 46, 44-200 Rybnik, Poland;
- Department of Internal Medicine, Diabetology, and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland;
| | - Monika Tarnawska
- Faculty of Natural Sciences, Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Bankowa 9, 40-007 Katowice, Poland; (M.T.); (P.Ł.)
| | - Elżbieta Chełmecka
- Department of Statistics, Department of Instrumental Analysis, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland;
| | - Piotr Łaszczyca
- Faculty of Natural Sciences, Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Bankowa 9, 40-007 Katowice, Poland; (M.T.); (P.Ł.)
| | - Janusz Gumprecht
- Department of Internal Medicine, Diabetology, and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland;
| | - Dominika Stygar
- Department of Physiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland
- Correspondence: ; Tel.: +48-32-272-23-62
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Chen W, Zhuang YS, Yang CX, Fang ZC, Liu BY, Zheng X, Liao YY. The Protective Role of the Long Pentraxin PTX3 in Spontaneously Hypertensive Rats with Heart Failure. Cardiovasc Toxicol 2021; 21:808-819. [PMID: 34173191 DOI: 10.1007/s12012-021-09671-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 06/17/2021] [Indexed: 10/21/2022]
Abstract
Pentraxin 3 (PTX3) is synthesized locally and released into the circulation, reflecting local inflammation in the cardiovascular system. Therefore, we conducted a study to explore the effect of PTX3 in spontaneously hypertensive heart failure (SHHF) rats. Sprague Dawley (SD) and SHHF rats were treated with recombinant PTX3 protein, and the blood pressure (BP) and echocardiographic parameters were collected. Radioimmunoassay, enzyme immunoassay and enzyme-linked immunosorbent assay (ELISA) were applied to detect plasma levels of atrial/B-type natriuretic peptide (ANP/BNP) and PTX3. The pathological changes in the myocardial tissues were observed by hematoxylin and eosin (HE) and Masson stainings. The mRNA and protein expressions were detected by quantitative real-time reverse-transcription polymerase chain reaction (qPCR) and western blotting. Cardiomyocyte apoptosis was evaluated by TUNEL staining and DNA fragmentation test. Increased plasma concentrations of PTX3 were found in SHHF rats compared with SD rats, which was further enhanced by recombinant PTX3 protein. After injection with recombinant PTX3 protein, the heart function was improved in SHHF rats with the decreased systolic and diastolic BP, and the reduced plasma levels of ANP and BNP. Moreover, PTX3 improved the myocardial damage and interstitial fibrosis in SHHF rats with reduced cardiomyocyte apoptosis and decreased mRNA expressions of pro-inflammatory factors in myocardial tissues. PTX3 could decrease the BP and plasma levels of ANP and BNP in SHHF rats, as well as improve the inflammation, cardiomyocyte apoptosis, and pathological changes of myocardial tissues, suggesting it may be a useful intervention in the treatment of SHHF.
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Affiliation(s)
- Wei Chen
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Ya-Se Zhuang
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Chun-Xia Yang
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Zhi-Cheng Fang
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Bo-Yi Liu
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Xiang Zheng
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Ying-Ying Liao
- Department of Gastroenterology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
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21
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Gürses D, Oğuz M, Yilmaz M, Aybek H, Akpinar F. Pentraxin 3 levels and correlation with disease severity in patients with acute rheumatic fever. Arch Rheumatol 2021; 36:233-243. [PMID: 34527928 PMCID: PMC8418760 DOI: 10.46497/archrheumatol.2021.8232] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 09/07/2020] [Indexed: 11/04/2022] Open
Abstract
Objectives
This study aims to investigate serum pentraxin 3 (PTX3) levels during acute episode of acute rheumatic fever (ARF) and their relationship with disease severity. Patients and methods
The prospective study was conducted between January 2015 and December 2018 and included 52 ARF patients (22 girls, 30 boys, mean age 10.7±2.1 years; range, 5 to 16 years) experiencing an acute episode and 22 healthy children (13 girls, 9 boys, mean age 10.3±3.8 years; range, 5 to 16 years). ARF patients were classified into three groups based on the clinical course: isolated arthritis (n=17), mild carditis (n=19), and moderate/severe carditis (n=16). Blood samples were collected from all patients before treatment and from the healthy children in the control group to measure PTX3 levels. PTX3 was measured using sandwich enzyme-linked immunosorbent assay method. Results
Plasma PTX3 levels were significantly higher in ARF group compared to the control group (4.7±5.2 and 1.2±1.7 ng/mL, p<0.001). Subgroup analysis of serum PTX3 levels in ARF patients with isolated arthritis, mild carditis, and moderate/severe carditis (3.2±3.1 ng/mL, 4.3±5 ng/mL, and 6.7±6.6 ng/mL, respectively) showed that serum PTX3 was significantly higher in the moderate/severe carditis group compared to the other groups (p<0.05). Analysis of echocardiographic data showed that serum PTX3 was positively correlated with left ventricular end-diastolic diameter, left atrial diameters, and mitral A velocity and negatively correlated with E/A ratio (p<0.05; r=0.231, 0.402, 0.562, -0.586, respectively). Conclusion High PTX3 level during an acute episode of ARF may help predict the clinical course and the severity of accompanying carditis. However, prospective studies with larger sample sizes are needed.
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Affiliation(s)
- Dolunay Gürses
- Department of Pediatric Cardiology, Pamukkale University Faculty of Medicine, Denizli, Turkey
| | - Merve Oğuz
- Department of Pediatrics, Pamukkale University Faculty of Medicine, Denizli, Turkey
| | - Münevver Yilmaz
- Department of Pediatric Cardiology, Pamukkale University Faculty of Medicine, Denizli, Turkey
| | - Hülya Aybek
- Department of Biochemistry, Pamukkale University Faculty of Medicine, Denizli, Turkey
| | - Funda Akpinar
- Department of Developmental and Behavioral Pediatrics, Ankara University Faculty of Medicine, Ankara, Turkey
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Chen W, Liu Y, Pan H, Jiang J, Xiang H, Peng L. Correlation between single nucleotide polymorphisms in the 3 primer untranslated region of PTX3 and the risk of essential hypertension: A case-control study. Medicine (Baltimore) 2021; 100:e25937. [PMID: 34128842 PMCID: PMC8213333 DOI: 10.1097/md.0000000000025937] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Accepted: 04/16/2021] [Indexed: 01/04/2023] Open
Abstract
The aim of this study was to investigate the correlation between single-nucleotide polymorphisms (SNPs) in the 3 primer of untranslated region (3'UTR) of the Pentraxin 3 (PTX3) gene and the risk of essential hypertension (EHT).PTX3 genotypes, rs2614, rs111451363, and rs73158510 locus, were found in 260 patients with EHT and 260 healthy controls. Quantitative real-time polymerase chain reaction was used to detect plasma hsa-miR-4766-5p levels. Enzyme-linked immunosorbent assay was used to detect plasma PTX3 levels. The dual-luciferase reporter assay was used to identify the binding site of hsa-miR-4766-5p to the PTX3.PTX3 rs2614 locus T allele was a high risk factor for EHT (odds ratio [OR] = 2.76, 95% confidence interval [CI]: 1.86-4.09, P < .01). Sex and diabetes history affected the correlation between PTX3 gene rs2614 locus SNP and EHT risk. The CCG haplotype was a protective factor for EHT (OR = 0.40, 95% CI: 0.28-0.57, P < .01), whereas the TCG haplotype was a risk factor for EHT (OR = 2.35, 95% CI: 1.51-3.66, P < .01). The plasma PTX3 level of patients with EHT was significantly higher than that of the control group, and the difference was statistically significant (P < .01). The area under the curve for EHT diagnosis in plasma PTX3 levels was 0.62 (95% CI: 0.57-0.66, P < .01). The plasma hsa-miR-4766-5p level in patients with EHT was significantly lower than that in the control group (P < .01). The area under the curve for the diagnosis of EHT according to the plasma hsa-miR-4766-5p level was 0.88 (95% CI: 0.85-0.91, P < .01). Plasma PTX3 levels were significantly negatively correlated with hsa-miR-4766-5p levels in patients with EHT and the control group (r = -0.87, -0.85, P < .01, P < .01). The PTX3 gene rs2614 locus C allele was the target gene of hsa-miR-4766-5p.The PTX3 rs2614 locus SNP is significantly associated with EHT risk.
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Affiliation(s)
| | | | | | | | - Huaqing Xiang
- Department of Ultrasound, Pujiang Branch of the First Affiliated Hospital, School of Medicine, Zhejiang University, Jinhua
| | - Linlin Peng
- Department of Clinical Laboratory, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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23
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Bonacina F, Pirillo A, Catapano AL, Norata GD. HDL in Immune-Inflammatory Responses: Implications beyond Cardiovascular Diseases. Cells 2021; 10:cells10051061. [PMID: 33947039 PMCID: PMC8146776 DOI: 10.3390/cells10051061] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/27/2021] [Accepted: 04/27/2021] [Indexed: 12/15/2022] Open
Abstract
High density lipoproteins (HDL) are heterogeneous particles composed by a vast array of proteins and lipids, mostly recognized for their cardiovascular (CV) protective effects. However, evidences from basic to clinical research have contributed to depict a role of HDL in the modulation of immune-inflammatory response thus paving the road to investigate their involvement in other diseases beyond those related to the CV system. HDL-C levels and HDL composition are indeed altered in patients with autoimmune diseases and usually associated to disease severity. At molecular levels, HDL have been shown to modulate the anti-inflammatory potential of endothelial cells and, by controlling the amount of cellular cholesterol, to interfere with the signaling through plasma membrane lipid rafts in immune cells. These findings, coupled to observations acquired from subjects carrying mutations in genes related to HDL system, have helped to elucidate the contribution of HDL beyond cholesterol efflux thus posing HDL-based therapies as a compelling interventional approach to limit the inflammatory burden of immune-inflammatory diseases.
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Affiliation(s)
- Fabrizia Bonacina
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy;
| | - Angela Pirillo
- Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, 20092 Milan, Italy;
- IRCCS MultiMedica, Sesto S. Giovanni, 20099 Milan, Italy
| | - Alberico L. Catapano
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy;
- IRCCS MultiMedica, Sesto S. Giovanni, 20099 Milan, Italy
- Correspondence: (A.L.C.); (G.D.N.)
| | - Giuseppe D. Norata
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy;
- Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, 20092 Milan, Italy;
- Correspondence: (A.L.C.); (G.D.N.)
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Demir I, Toker A, Aksoy H, Tasyurek E, Zengin S. The Impact of Shift Type on Oxidative Stress, Inflammation, and Platelet Activation. J Occup Environ Med 2021; 63:e127-e131. [PMID: 33652448 DOI: 10.1097/jom.0000000000002124] [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: 11/25/2022]
Abstract
OBJECTIVE Rotating shift is known to disrupt circadian rhythms. The 12/24 shift system, with frequent day-night rotations and the ergonomic shift system (ESS), with 90% less rotations were compared for their impacts on oxidative stress, inflammation, and platelet activation by using pentraxin 3 (PTX3), urinary 15-isoprostane F2t, and 11-dehydrotromboxane B2 (11-DTB2). METHODS All tests were performed by enzyme linked immunosorbent assay (ELISA). Unpaired t test and Pearson correlation analysis were employed. RESULTS Two hundred twenty 12/24 and 198 ESS workers were included. Plasma PTX3 and urinary 15-isoprostane F2t levels were not different between groups. Urinary 11-DTB2 in 12/24 workers were found significantly higher compared with ESS workers (P < 0.0001). A weak but significant correlation was found between urinary 15-isoprostane F2t and urinary 11-DTB2 levels (r = 0.17, P = 0.001). CONCLUSIONS 12/24 rotating shift was found to cause platelet activation disturbances.
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Affiliation(s)
- Irfan Demir
- Independent Researcher (Dr Demir, Dr Aksoy, Dr Zengin); Hipokrat Laboratories, Department of Biochemistry, Istanbul (Dr Toker); Community Health Center, Karaman (Dr Tasyurek), Turkey
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25
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Chen YT, Wang HH, Liu PY. Pentraxin 3: A Biomarker Link between Inflammation and Cardiovascular Risk among Obese Children. ACTA CARDIOLOGICA SINICA 2021; 37:184-185. [PMID: 33716460 PMCID: PMC7953117 DOI: 10.6515/acs.202103_37(2).20210122a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 01/22/2021] [Indexed: 11/23/2022]
Affiliation(s)
| | - Hui-Hsuan Wang
- Institute of Clinical Medicine, College of Medicine
- Department of Biochemistry and Molecular Biology, National Cheng Kung University
| | - Ping-Yen Liu
- Institute of Clinical Medicine, College of Medicine
- Division of Cardiology, Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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26
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Slusher AL, Fico BG, Dodge KM, Garten RS, Ferrandi PJ, Rodriguez AA, Pena G, Huang CJ. Impact of acute high-intensity interval exercise on plasma pentraxin 3 and endothelial function in obese individuals-a pilot study. Eur J Appl Physiol 2021; 121:1567-1577. [PMID: 33638689 DOI: 10.1007/s00421-021-04632-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 02/05/2021] [Indexed: 12/11/2022]
Abstract
PURPOSE Pentraxin 3 (PTX3) has been shown to be a predictor of endothelial dysfunction in patients with increased risk of cardiovascular disease (CVD) (e.g., obesity). Circulating PTX3 concentrations are dysregulated in obese individuals and are elevated following acute aerobic exercise. High-intensity interval exercise (HIIE) has been demonstrated to be as effective as continuous moderate-intensity exercise in improving endothelial function, as indicated by brachial artery flow-mediated dilation (BAFMD), in patients with CVD. Therefore, the purpose of this study was to examine the effect of acute HIIE on plasma PTX3 and BAFMD responses in obese individuals. METHODS Eight obese and six normal-weight young males participated in acute HIIE (4 intervals of 4 min at 80-90% of VO2max; 3 min of active recovery at 50-60% VO2max). Plasma PTX3 and BAFMD were measured prior to, immediately following exercise, and one and 2 hours into recovery. RESULTS Plasma PTX3 concentrations significantly increased following HIIE, yet the PTX3 response to HIIE was significantly blunted in obese compared to normal-weight participants. While the kinetic responses of BAFMD were also significantly different in obese compared to normal-weight participants, similar increases above the baseline were observed 2 hours into recovery in both groups. Finally, plasma PTX3 concentrations were not associated with BAFMD at baseline or in response to HIIE. CONCLUSION The utilization of HIIE may serve as a time-efficient exercise prescription strategy to transiently improve endothelial function, independent of elevated plasma PTX3 concentrations, in obese individuals.
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Affiliation(s)
- Aaron L Slusher
- School of Kinesiology, University of Michigan, Ann Arbor, MI, 48109, USA.
| | - Brandon G Fico
- Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, TX, 78712, USA
| | - Katelyn M Dodge
- Exercise Biochemistry Laboratory, Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, 33431, USA
| | - Ryan S Garten
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, VA, 23284, USA
| | - Peter J Ferrandi
- College of Graduate Health Sciences, The University of Tennessee Health Science Center, Memphis, TN, 38163, USA
| | - Alexandra A Rodriguez
- Exercise Biochemistry Laboratory, Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, 33431, USA
| | - Gabriel Pena
- Department of Kinesiology, University of Maryland-College Park, College Park, MD, 20742, USA
| | - Chun-Jung Huang
- Exercise Biochemistry Laboratory, Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, 33431, USA
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27
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Qiu C, Han Y, Zhang H, Liu T, Hou H, Luo D, Yu M, Bian K, Zhao Y, Xiao X. Perspectives on long pentraxin 3 and rheumatoid arthritis: several potential breakthrough points relying on study foundation of the past. Int J Med Sci 2021; 18:1886-1898. [PMID: 33746606 PMCID: PMC7976587 DOI: 10.7150/ijms.54787] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 01/24/2021] [Indexed: 12/27/2022] Open
Abstract
Rheumatoid arthritis (RA) is a systemic chronic autoimmune inflammatory disease which is mainly characterized by synovitis and results in a severe burden for both the individual and society. To date, the underlying mechanisms of RA are still poorly understood. Pentraxin 3 (PTX3) is a typical long pentraxin protein which has been highly conserved during evolution. Meanwhile, functions as well as properties of PTX3 have been extensively studied. Several studies identified that PTX3 plays a predominate role in infection, inflammation, immunity and tumor. Interestingly, PTX3 has also been verified to be closely associated with development of RA. We therefore accomplished an elaboration of the relationships between PTX3 and RA. Herein, we mainly focus on the associated cell types and cognate cytokines involved in RA, in combination with PTX3. This review infers the insight into the interaction of PTX3 in RA and aims to provide novel clues for potential therapeutic target of RA in clinic.
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Affiliation(s)
- Cheng Qiu
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P. R. China.,Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China.,Department of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China
| | - Yichao Han
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P. R. China.,Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China
| | - Hanwen Zhang
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P. R. China.,Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China
| | - Tianyi Liu
- Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China
| | - Haodong Hou
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P. R. China.,Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China
| | - Dan Luo
- College of Stomatology, Qingdao University, Qingdao 266071, Shandong, P. R. China
| | - Mingzhi Yu
- Key Laboratory of High Efficiency and Clean Manufacturing, School of Mechanical Engineering, Shandong University, Jinan 250061, Shandong, P. R. China
| | - Kai Bian
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P. R. China.,Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China
| | - Yunpeng Zhao
- Department of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, P. R. China
| | - Xing Xiao
- Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, P. R. China
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Truong R, Thankam FG, Agrawal DK. Immunological mechanisms underlying sterile inflammation in the pathogenesis of atherosclerosis: potential sites for intervention. Expert Rev Clin Immunol 2020; 17:37-50. [PMID: 33280442 DOI: 10.1080/1744666x.2020.1860757] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Introduction: Innate and adaptive immunity play a critical role in the underlying pathological mechanisms of atherosclerosis and potential target sites of sterile inflammation open opportunities to develop novel therapeutics. In response to oxidized LDL in the intimal layer, T cell subsets are recruited and activated at the site of atheroma to upregulate pro-atherogenic cytokines which exacerbate plaque formation instability.Areas covered: A systematic search of PubMed and the Web of Science was performed between January 2001- September 2020 and relevant articles in sterile inflammation and atherosclerosis were critically reviewed. The original information was collected on the interconnection between danger associated molecular patterns (DAMPs) as the mediators of sterile inflammation and the receptor complex of CD36-TLR4-TLR6 that primes and activates inflammasomes in the pathophysiology of atherosclerosis. Mediators of sterile inflammation are identified to target therapeutic strategies in the management of atherosclerosis.Expert opinion: Sterile inflammation via NLRP3 inflammasome is perpetuated by the activation of IL-1β and IL-18 and induction of pyroptosis resulting in the release of additional inflammatory cytokines and DAMPs. Challenges with current inhibitors of the NLRP3 inflammasome lie in the specificity, stability, and efficacy in targeting the NLRP3 inflammasome constituents without ameliorating upstream or downstream responses necessary for survival.
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Affiliation(s)
- Roland Truong
- Department of Translational Research, Western University of Health Sciences, Pomona, CA, USA
| | - Finosh G Thankam
- Department of Translational Research, Western University of Health Sciences, Pomona, CA, USA
| | - Devendra K Agrawal
- Department of Translational Research, Western University of Health Sciences, Pomona, CA, USA
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Meri S, Haapasalo K. Function and Dysfunction of Complement Factor H During Formation of Lipid-Rich Deposits. Front Immunol 2020; 11:611830. [PMID: 33363547 PMCID: PMC7753009 DOI: 10.3389/fimmu.2020.611830] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 11/09/2020] [Indexed: 01/19/2023] Open
Abstract
Complement-mediated inflammation or dysregulation in lipid metabolism are associated with the pathogenesis of several diseases. These include age-related macular degeneration (AMD), C3 glomerulonephritis (C3GN), dense deposit disease (DDD), atherosclerosis, and Alzheimer's disease (AD). In all these diseases, formation of characteristic lipid-rich deposits is evident. Here, we will discuss molecular mechanisms whereby dysfunction of complement, and especially of its key regulator factor H, could be involved in lipid accumulation and related inflammation. The genetic associations to factor H polymorphisms, the role of factor H in the resolution of inflammation in lipid-rich deposits, modification of macrophage functions, and complement-mediated clearance of apoptotic and damaged cells indicate that the function of factor H is crucial in limiting inflammation in these diseases.
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Affiliation(s)
- Seppo Meri
- Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
- Department of Bacteriology and Immunology, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
| | - Karita Haapasalo
- Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland
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30
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Dekker M, Waissi F, Timmerman N, Silvis MJM, Timmers L, de Kleijn DPV. Extracellular Vesicles in Diagnosing Chronic Coronary Syndromes the Bumpy Road to Clinical Implementation. Int J Mol Sci 2020; 21:E9128. [PMID: 33266227 PMCID: PMC7729611 DOI: 10.3390/ijms21239128] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 11/26/2020] [Accepted: 11/28/2020] [Indexed: 12/15/2022] Open
Abstract
Coronary artery disease (CAD), comprising both acute coronary syndromes (ACS) and chronic coronary syndromes (CCS), remains one of the most important killers throughout the entire world. ACS is often quickly diagnosed by either deviation on an electrocardiogram or elevated levels of troponin, but CCS appears to be more complicated. The most used noninvasive strategies to diagnose CCS are coronary computed tomography and perfusion imaging. Although both show reasonable accuracy (80-90%), these modalities are becoming more and more subject of debate due to costs, radiation and increasing inappropriate use in low-risk patients. A reliable, blood-based biomarker is not available for CCS but would be of great clinical importance. Extracellular vesicles (EVs) are lipid-bilayer membrane vesicles containing bioactive contents e.g., proteins, lipids and nucleic acids. EVs are often referred to as the "liquid biopsy" since their contents reflect changes in the condition of the cell they originate from. Although EVs are studied extensively for their role as biomarkers in the cardiovascular field during the last decade, they are still not incorporated into clinical practice in this field. This review provides an overview on EV biomarkers in CCS and discusses the clinical and technological aspects important for successful clinical application of EVs.
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Affiliation(s)
- Mirthe Dekker
- Department of Vascular Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; (M.D.); (F.W.); (N.T.)
- Department of Cardiology, Amsterdam University Medical Centre, Mijbergdreef 9, 1105AZ Amsterdam, The Netherlands
| | - Farahnaz Waissi
- Department of Vascular Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; (M.D.); (F.W.); (N.T.)
- Department of Cardiology, Amsterdam University Medical Centre, Mijbergdreef 9, 1105AZ Amsterdam, The Netherlands
| | - Nathalie Timmerman
- Department of Vascular Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; (M.D.); (F.W.); (N.T.)
| | - Max J. M. Silvis
- Department of Cardiology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands;
| | - Leo Timmers
- Department of Cardiology, St. Antonius Hospital Nieuwegein, 3435 CM Nieuwegein, The Netherlands;
| | - Dominique P. V. de Kleijn
- Department of Vascular Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands; (M.D.); (F.W.); (N.T.)
- Netherlands Heart Institute, 3511 EP Utrecht, The Netherlands
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WU W, XU J. [Research progress on the role of pentraxin 3 in polycystic ovary syndrome]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2020; 49:637-643. [PMID: 33210493 PMCID: PMC8800715 DOI: 10.3785/j.issn.1008-9292.2020.08.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 04/23/2020] [Indexed: 06/11/2023]
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disease of child-bearing period women and one of the main causes of infertility in women. Pentraxin 3 (PTX3) is a multifunctional protein with a series of biological activities. PTX3 participates in the regulation of insulin secretion and glucose metabolism, ovarian cumulus cell function, inflammatory factor activity, androgen metabolism, lipid absorption and transport, and endothelial cell function, thereby improving insulin resistance, promoting follicular development and ovulation, reducing chronic inflammation, inhibiting androgen levels, improving lipid metabolism abnormalities and preventing atherosclerosis and cardiovascular diseases, thus participating in the occurrence of PCOS and its complications. This article reviews the mechanism of PTX3 in PCOS and its complications, trying to provide new ideas and directions for the study of PCOS pathogenesis and its clinical diagnosis and treatment.
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Affiliation(s)
| | - Jian XU
- 徐键(1961-), 男, 博士, 主任医师, 博士生导师, 主要从事生殖医学与妇科内分泌、辅助生育技术、妇科内窥镜研究; E-mail:
;
https://orcid.org/0000-0002-0307-3198
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Roche-Molina M, Hardwick B, Sanchez-Ramos C, Sanz-Rosa D, Gewert D, Cruz FM, Gonzalez-Guerra A, Andres V, Palma JA, Ibanez B, Mckenzie G, Bernal JA. The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis. Sci Rep 2020; 10:11636. [PMID: 32669659 PMCID: PMC7363918 DOI: 10.1038/s41598-020-68350-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 06/19/2020] [Indexed: 12/25/2022] Open
Abstract
N-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It is used as a drug solubilizer and penetration enhancer in human and animal, yet its bioactivity properties remain elusive. Here, we report that NMP is a bioactive anti-inflammatory compound well tolerated in vivo, that shows efficacy in reducing disease in a mouse model of atherosclerosis. Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Monocytes and endothelial cells treated with NMP express increased levels of KLF2, produce less pro-inflammatory cytokines and adhesion molecules. We found that NMP attenuates monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha (TNF-α) by reducing expression of adhesion molecules. We further show using KLF2 shRNA that the inhibitory effect of NMP on endothelial inflammation and subsequent monocyte adhesion is KLF2 dependent. Enhancing KLF2 expression and activity improves endothelial function, controls multiple genes critical for inflammation, and prevents atherosclerosis. Our findings demonstrate a consistent effect of NMP upon KLF2 activation and inflammation, biological processes central to atherogenesis. Our data suggest that inclusion of bioactive solvent NMP in pharmaceutical compositions to treat inflammatory disorders might be beneficial and safe, in particular to treat diseases of the vascular system, such as atherosclerosis.
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Affiliation(s)
- Marta Roche-Molina
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain
| | - Bryn Hardwick
- MRC Cancer Unit At the University of Cambridge, Hutchison/MRC Research Centre, Box 197, Biomedical Campus, Hills Road, Cambridge, CB2 0XZ, UK
| | - Cristina Sanchez-Ramos
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain
| | - David Sanz-Rosa
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain.,CIBERCV, Madrid, Spain.,Department of Medicine, Universidad Europea de Madrid, Madrid, Spain
| | - Dirk Gewert
- DG Bioconsult Ltd, 50 Gilbert Road, Cambridge, CB4 3PE, UK
| | - Francisco M Cruz
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain
| | - Andres Gonzalez-Guerra
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain
| | - Vicente Andres
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain.,CIBERCV, Madrid, Spain
| | - Joaquin A Palma
- Department of Development, Grupo STIG, Velázquez 11, 28001, Madrid, CP, Spain
| | - Borja Ibanez
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain.,CIBERCV, Madrid, Spain.,IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain
| | - Grahame Mckenzie
- MRC Cancer Unit At the University of Cambridge, Hutchison/MRC Research Centre, Box 197, Biomedical Campus, Hills Road, Cambridge, CB2 0XZ, UK.
| | - Juan A Bernal
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro 3, CP28029, Madrid, Spain. .,CIBERCV, Madrid, Spain.
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Pathophysiological and Genetic Aspects of Vascular Calcification. Cardiol Res Pract 2020; 2020:5169069. [PMID: 32411445 PMCID: PMC7201852 DOI: 10.1155/2020/5169069] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 02/17/2020] [Accepted: 03/23/2020] [Indexed: 12/21/2022] Open
Abstract
Recent evidence suggests that vascular calcification is an independent cardiovascular risk factor (CRF) of morbidity and mortality. New studies point out the existence of a complex physiopathological mechanism that involves inflammation, oxidation, the release of chemical mediators, and genetic factors that promote the osteochondrogenic differentiation of vascular smooth muscle cells (VSMC). This review will evaluate the main mechanisms involved in the pathophysiology and genetics modulation of the process of vascular calcification. Objective. A systematic review of the pathophysiology factors involved in vascular calcification and its genetic influence was performed. Methods. A systematic review was conducted in the Medline and PubMed databases and were searched for studies concerning vascular calcification using the keywords and studies published until 2020/01 in English. Inclusion Criteria. Studies in vitro, animal models, and humans. These include cohort (both retrospective and prospective cohort studies), case-control, cross-sectional, and systematic reviews. Exclusion Criteria. Studies before 2003 of the existing literature.
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Pentraxin 3 (PTX3): A Molecular Marker of Endothelial Dysfunction in Chronic Migraine. J Clin Med 2020; 9:jcm9030849. [PMID: 32244987 PMCID: PMC7141491 DOI: 10.3390/jcm9030849] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/09/2020] [Accepted: 03/18/2020] [Indexed: 01/03/2023] Open
Abstract
Even though endothelial dysfunction is known to play a role in migraine pathophysiology, studies regarding levels of endothelial biomarkers in migraine have controversial results. Our aim was to evaluate the role of pentraxin 3 (PTX3) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) as potential biomarkers of endothelial dysfunction in chronic migraine (CM). We performed a case-control study including 102 CM patients and 28 control subjects and measured serum levels of markers of endothelial dysfunction (PTX3 and sTWEAK) and inflammation [high-sensitivity C-reactive protein (hs-CRP)] as well as brachial artery flow-mediated dilation (FMD) during interictal periods. Interictal serum levels of PTX3 and sTWEAK were higher in CM patients than in controls (1350.6 ± 54.8 versus 476.1 ± 49.4 pg/mL, p < 0.001 and 255.7 ± 21.1 versus 26.4 ± 2.6 pg/mL, p < 0.0001; respectively). FMD was diminished in CM patients compared to controls (9.6 ± 0.6 versus 15.2 ± 0.9%, p < 0.001). Both PTX3 and sTWEAK were negatively correlated with FMD (r = −0.508, p < 0.001 and r = −0.188, p = 0.033; respectively). After adjustment of confounders, PTX3 remained significantly correlated to FMD (r = −0.250, p = 0.013). Diagnosis of CM was 68.4 times more likely in an individual with levels of PTX3 ≥ 832.5 pg/mL, suggesting that PTX3 could be a novel biomarker of endothelial dysfunction in CM.
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Silencing of PTX3 alleviates LPS-induced inflammatory pain by regulating TLR4/NF-κB signaling pathway in mice. Biosci Rep 2020; 40:221905. [PMID: 31957804 PMCID: PMC7000368 DOI: 10.1042/bsr20194208] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 01/07/2020] [Accepted: 01/09/2020] [Indexed: 02/03/2023] Open
Abstract
Pentraxin 3 (PTX3), an inflammatory marker and a pattern recognition receptor, plays an important role in promoting the progress of tumor and inflammatory diseases. However, the role of PTX3 in the pathogenesis of inflammatory pain diseases is rarely reported. The purpose of the present study is to investigate the effect of PTX3 on the progression of inflammatory pain and the special molecular mechanism. A mouse BV2 microglia cell activation-mediated inflammatory model was developed with Lipopolysaccharide (LPS) induction, and a mouse inflammatory pain model was established with LPS injection. The effect of PTX3 on microglia inflammatory activation was verified by measuring pro-inflammatory cytokines expression. The mechanical hyperalgesia testing, the thermal preference testing and the cold allodynia testing were used to measure the response of mice to mechanical pain, heat stimulation and cold stimulation, respectively. The results revealed that the expression of PTX3 was decreased in the LPS-induced inflammatory pain mice model. Silencing of PTX3 down-regulated LPS-induced inflammatory factors, including IL-6, NO and TNF-α, and alleviated LPS-induced inflammatory pain in BV2 cells. In addition, overexpression of TLR4 reversed the inhibitory effect of si-PTX3 on LPS-induced inflammatory response in BV2 cells. What is more, silencing of PTX3 inhibited TLR4/NF-κB signaling pathway. Collectively, it suggests that silencing of PTX3 alleviates LPS-induced inflammatory response of BV2 cells potentially by regulating the TLR4/NF-κB signaling pathway.
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Relationship of systemic pentraxin-3 values with coronary plaque components on optical coherence tomography and post-percutaneous coronary intervention outcomes in patients with stable angina pectoris. Atherosclerosis 2020; 292:127-135. [DOI: 10.1016/j.atherosclerosis.2019.11.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 10/25/2019] [Accepted: 11/27/2019] [Indexed: 11/20/2022]
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Tonial AF, Nisihara R, Nassif PAN, Munhoz SI, Cortina AG, Gobetti JSC, Skare T. Bariatric surgery results in restoration of physiological plasma levels of pentraxine-3. Biomed Rep 2019; 12:68-72. [PMID: 31929876 DOI: 10.3892/br.2019.1264] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 11/10/2019] [Indexed: 12/17/2022] Open
Abstract
Pentraxine-3 (PTX3) is a member of the humoral innate immune system and serves a role in protection against infections, inflammation control and matrix deposition. The aim of the present study was to measure the PTX3 levels in obese patients and its association with glycemic and lipid profiles, and to analyze the effects of weight loss provided by bariatric surgery in serum PTX3 levels. PTX3 was measured in 84 obese patients whom underwent bariatric surgery and 94 healthy controls. Lipid and glycemic profiles were determined using a clinical chemistry analyzer, and PTX3 levels were measured in patients prior to and following bariatric surgery using ELISA. PTX3 levels prior to surgery were significantly lower compared with the normal controls (median of 0.10 vs. 0.80 ng/ml; P<0.0001). Following surgery, the median weight loss was 33.1 kg, and the median PTX3 levels were significantly increased to 1.45 ng/ml compared with pre-surgery levels (P<0.001) and did not differ significantly from the control group levels (P=0.10). There were no correlations between PTX3 levels and total cholesterol, HDL and LDL, fasting glycemia, HbA1c and basal insulin levels. A significant positive correlation was observed between PTX3 levels and triglycerides levels in the post-operative period (ρ=0.26, P=0.01). In conclusion, obese patients had lower levels of PTX3 compared with the control patients, and the levels were restored to physiological levels following bariatric surgery which may be associated with the weight loss.
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Affiliation(s)
- Alessandro F Tonial
- Medical Research Institute, Evangelical Mackenzie University, Curitiba, Paraná 80730-000, Brazil
| | - Renato Nisihara
- Department of Medicine, Mackenzie Evangelical School of Medicine Paraná, Curitiba, Paraná 80730-000, Brazil.,Department of Medicine, Positivo University, Curitiba, Paraná 80730-000, Brazil
| | - Paulo A N Nassif
- Medical Research Institute, Evangelical Mackenzie University, Curitiba, Paraná 80730-000, Brazil.,Department of Medicine, Mackenzie Evangelical School of Medicine Paraná, Curitiba, Paraná 80730-000, Brazil
| | - Sofia I Munhoz
- Department of Medicine, Mackenzie Evangelical School of Medicine Paraná, Curitiba, Paraná 80730-000, Brazil
| | - Alex G Cortina
- Department of Medicine, Mackenzie Evangelical School of Medicine Paraná, Curitiba, Paraná 80730-000, Brazil
| | - Júlia S C Gobetti
- Department of Medicine, Mackenzie Evangelical School of Medicine Paraná, Curitiba, Paraná 80730-000, Brazil
| | - Thelma Skare
- Medical Research Institute, Evangelical Mackenzie University, Curitiba, Paraná 80730-000, Brazil.,Department of Medicine, Mackenzie Evangelical School of Medicine Paraná, Curitiba, Paraná 80730-000, Brazil
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38
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Benhuri B, ELJack A, Kahaleh B, Chakravarti R. Mechanism and biomarkers in aortitis--a review. J Mol Med (Berl) 2019; 98:11-23. [PMID: 31664480 DOI: 10.1007/s00109-019-01838-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 09/11/2019] [Accepted: 09/22/2019] [Indexed: 12/26/2022]
Abstract
Aortitis can be the manifestation of an underlying infectious or noninfectious disease process. An autoimmune cause is suggested in a large proportion of noninfectious causes. Similar to other autoimmune diseases, the pathophysiology of aortitis has been investigated in detail, but the etiology remains unknown. Most cases of aortitis often go undetected for a long time and are often identified at late stages of the disease. Recent advances in imaging techniques have significantly improved the diagnosis of aortitis. However, significant challenges associated with the imaging techniques limit their use. Several routine inflammation-based markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and inflammatory cytokines, are nonspecific and, therefore, have limited use in the diagnosis of aortitis. The search for more specific serum biomarkers, which can facilitate detection and progression is under progress. Several autoantibodies have been identified, but assigning their role in the pathogenesis as well as their specificity remains a challenge. The current review addresses some of these issues in detail. KEY MESSAGES: • Noninfectious aortitis is an autoimmune disease. • Several biomarkers, including cytokines and autoantibodies, are increased in aortitis. • Imaging techniques, commonly used to detect aortitis, are associated with the high cost and technical challenges. • There is a need to develop low-cost biomarker-based detection tools. • The knowledge of biomarkers in aortitis detection is discussed.
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Affiliation(s)
- Benjamin Benhuri
- Department of Physiology & Pharmacology, College of Medical & Life Sciences, University of Toledo College of Medicine, 3000 Arlington Ave, Toledo, OH, 43614, USA.,Department of Internal Medicine, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ammar ELJack
- Department of Physiology & Pharmacology, College of Medical & Life Sciences, University of Toledo College of Medicine, 3000 Arlington Ave, Toledo, OH, 43614, USA.,Depatment of Intenal Medicine, Beaumont Hospital, Dearborn, MI, 48124, USA
| | - Bashar Kahaleh
- Division of Rheumatology, University of Toledo College of Medicine, 3000 Arlington Ave, Toledo, OH, 43614, USA
| | - Ritu Chakravarti
- Department of Physiology & Pharmacology, College of Medical & Life Sciences, University of Toledo College of Medicine, 3000 Arlington Ave, Toledo, OH, 43614, USA.
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Slusher AL, Zúñiga TM, Acevedo EO. Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT following LPS Stimulation. Mediators Inflamm 2019; 2019:2324193. [PMID: 31611733 PMCID: PMC6757284 DOI: 10.1155/2019/2324193] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 05/22/2019] [Accepted: 06/20/2019] [Indexed: 12/31/2022] Open
Abstract
Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p ≤ 0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p = 0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r = -0.404, p = 0.027; r = -0.427, p = 0.019; and r = -0.323, p = 0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p = 0.033) and negatively associated with telomere lengths (r = 0.353, p = 0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.
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Affiliation(s)
- Aaron L. Slusher
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, VA, USA
- School of Kinesiology, University of Michigan, Ann Arbor, MI, USA
| | - Tiffany M. Zúñiga
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, VA, USA
- Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA
| | - Edmund O. Acevedo
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, VA, USA
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de Oliveira THC, Souza DG, Teixeira MM, Amaral FA. Tissue Dependent Role of PTX3 During Ischemia-Reperfusion Injury. Front Immunol 2019; 10:1461. [PMID: 31354697 PMCID: PMC6635462 DOI: 10.3389/fimmu.2019.01461] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 06/10/2019] [Indexed: 01/06/2023] Open
Abstract
Reperfusion of an ischemic tissue is the treatment of choice for several diseases, including myocardial infarction and stroke. However, reperfusion of an ischemic tissue causes injury, known as Ischemia and Reperfusion Injury (IRI), that limits the benefit of blood flow restoration. IRI also occurs during solid organ transplantation. During IRI, there is activation of the innate immune system, especially neutrophils, which contributes to the degree of injury. It has been shown that PTX3 can regulate multiple aspects of innate immunity and tissue inflammation during sterile injury, as observed during IRI. In humans, levels of PTX3 increase in blood and elevated levels associate with extent of IRI. In mice, there is also enhanced expression of PTX3 in tissues and plasma after IRI. In general, absence of PTX3, as seen in PTX3-deficient mice, results in worse outcome after IRI. On the contrary, increased expression of PTX3, as seen in PTX3 transgenic mice and after PTX3 administration, is associated with better outcome after IRI. The exception is the gut where PTX3 seems to have a clear deleterious role. Here, we discuss mechanisms by which PTX3 contributes to IRI and the potential of taming this system for the treatment of injuries associated with reperfusion of solid organs.
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Affiliation(s)
| | - Danielle G Souza
- Host-Microorganism Interaction Laboratory, Department of Microbiology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Mauro Martins Teixeira
- Immunopharmacology Laboratory, Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Flávio Almeida Amaral
- Immunopharmacology Laboratory, Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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Long Pentraxin 3 as a Broader Biomarker for Multiple Risk Factors in End-Stage Renal Disease: Association with All-Cause Mortality. Mediators Inflamm 2019; 2019:3295725. [PMID: 31316299 PMCID: PMC6604294 DOI: 10.1155/2019/3295725] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 05/06/2019] [Indexed: 12/29/2022] Open
Abstract
Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD.
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Vyas V, Paula Longhi M. Pentraxin 3: a novel target in the obesity–inflammation cascade. Cardiovasc Res 2019; 115:1811-1812. [DOI: 10.1093/cvr/cvz146] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Vishal Vyas
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Maria Paula Longhi
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Strunk D, Schmidt-Pogoda A, Beuker C, Milles LS, Korsukewitz C, Meuth SG, Minnerup J. Biomarkers in Vasculitides of the Nervous System. Front Neurol 2019; 10:591. [PMID: 31244756 PMCID: PMC6562258 DOI: 10.3389/fneur.2019.00591] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Accepted: 05/20/2019] [Indexed: 12/13/2022] Open
Abstract
Besides being affected by the rare and severe primary angiitis of the central nervous system (PACNS) the nervous system is also affected by primary systemic vasculitides (PSV). In contrast to PACNS, PSV affect not only the central but also the peripheral nervous system, resulting in a large array of potential symptoms. Given the high burden of disease, difficulties in distinguishing between differential diagnoses, and incomplete pathophysiological insights, there is an urgent need for additional precise diagnostic tools to enable an earlier diagnosis and initiation of effective treatments. Methods available to date, such as inflammatory markers, antibodies, cerebrospinal fluid (CSF) analysis, imaging, and biopsy, turn out to be insufficient to meet all current challenges. We highlight the use of biomarkers as an approach to extend current knowledge and, ultimately, improve patient management. Biomarkers are considered to be useful for disease diagnosis and monitoring, for predicting response to treatment, and for prognosis in clinical practice, as well as for establishing outcome parameters in clinical trials. In this article, we review the recent literature on biomarkers which have been applied in the context of different types of nervous system vasculitides including PACNS, giant-cell arteritis, Takayasu's arteritis, polyarteritis nodosa, ANCA (anti-neutrophil cytoplasm antibody)-associated vasculitides, cryoglobulinemic vasculitis, IgA vasculitis, and Behçet's disease. Overall, the majority of biomarkers is not specific for vasculitides of the nervous system.
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Affiliation(s)
- Daniel Strunk
- Department of Neurology, Institute for Translational Neurology, University of Münster, Münster, Germany
| | - Antje Schmidt-Pogoda
- Department of Neurology, Institute for Translational Neurology, University of Münster, Münster, Germany
| | - Carolin Beuker
- Department of Neurology, Institute for Translational Neurology, University of Münster, Münster, Germany
| | - Lennart S Milles
- Department of Neurology, Institute for Translational Neurology, University of Münster, Münster, Germany
| | - Catharina Korsukewitz
- Department of Neurology, Institute for Translational Neurology, University of Münster, Münster, Germany
| | - Sven G Meuth
- Department of Neurology, Institute for Translational Neurology, University of Münster, Münster, Germany
| | - Jens Minnerup
- Department of Neurology, Institute for Translational Neurology, University of Münster, Münster, Germany
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Kontny F, Andersen T, Ueland T, Åkerblom A, Lakic TG, Michelsen AE, Aukrust P, Bertilsson M, Becker RC, Himmelmann A, James SK, Siegbahn A, Storey RF, Wallentin L. Pentraxin-3 vs C-reactive protein and other prognostic biomarkers in acute coronary syndrome: A substudy of the Platelet Inhibition and Patients Outcomes (PLATO) trial. EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE 2019; 9:313-322. [PMID: 31017470 DOI: 10.1177/2048872619846334] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
AIMS We investigated the dynamics, associations with patient characteristics, other biomarkers, and clinical outcomes of pentraxin 3 in acute coronary syndrome. METHODS AND RESULTS In multivariate analyses, pentraxin 3 measured in 5154 patients randomised in the Platelet Inhibition and Patients Outcomes (PLATO) trial (NCT00391872) was compared with leukocytes, high-sensitivity C-reactive protein, interleukin-6, cystatin C, N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15 concerning prediction of clinical outcome. Pentraxin 3 peaked earlier than high-sensitivity C-reactive protein and was more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein. The frequency of cardiovascular death, spontaneous myocardial infarction or stroke by quartiles of pentraxin 3 at admission was 6.1%, 7.3%, 9.7% and 10.7%, respectively (p<0.0001). The hazard ratio per 50% increase of pentraxin 3 was 1.13 (95% confidence interval: 1.07-1.19), p<0.0001. This association remained significant after stepwise adjustments for leukocytes/high-sensitivity C-reactive protein (1.09 (1.02-1.15)), p=0.009, interleukin-6 (1.07 (1.01-1.14)), p=0.026, and cystatin C (1.07 (1.00-1.13)), p=0.044, but not after adjustment for N-terminal prohormone brain natriuretic peptide, high-sensitivity troponin T and growth differentiation factor 15. Admission pentraxin 3 was also associated with several of the individual endpoint components (cardiovascular death/spontaneous myocardial infarction; p=0.008, cardiovascular death; p=0.026, and spontaneous myocardial infarction; p=0.017), but not with stroke. Pentraxin 3 measured in the chronic phase (i.e. at one month) was still predictive of the composite endpoint in univariate analysis (1.12 (1.04-1.20) per 50% increase) p=0.0024, but not after adjustment for the other biomarkers. CONCLUSION Admission level of pentraxin 3 is a modestly stronger predictor than high-sensitivity C-reactive protein and interleukin-6, but not than N-terminal prohormone brain natriuretic peptide or high-sensitivity troponin T, concerning cardiovascular outcome in acute coronary syndrome. Pentraxin 3 is more strongly correlated with N-terminal prohormone brain natriuretic peptide and high-sensitivity troponin T than with high-sensitivity C-reactive protein.
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Affiliation(s)
- Frederic Kontny
- Department of Cardiology, Stavanger University Hospital, Norway.,Drammen Heart Center, Norway
| | - Thomas Andersen
- Department of Anaesthesiology, Stavanger University Hospital, Norway
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway.,K.G. Jebsen Thrombosis Research and Expertise Center (TREC), University of Tromsø, Norway
| | - Axel Åkerblom
- Department of Medical Sciences, Cardiology Uppsala University, Sweden.,Uppsala Clinical Research Center, Uppsala University, Sweden
| | - Tatevik G Lakic
- Uppsala Clinical Research Center, Uppsala University, Sweden
| | - Annika E Michelsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway.,K.G. Jebsen Thrombosis Research and Expertise Center (TREC), University of Tromsø, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Norway.,K.G. Jebsen Thrombosis Research and Expertise Center (TREC), University of Tromsø, Norway.,Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Norway
| | | | - Richard C Becker
- Division of Cardiovascular Health and Disease, Academic Health Center, Cincinnati, OH, USA
| | | | - Stefan K James
- Department of Medical Sciences, Cardiology Uppsala University, Sweden.,Uppsala Clinical Research Center, Uppsala University, Sweden
| | - Agneta Siegbahn
- Department of Medical Sciences, Cardiology Uppsala University, Sweden.,Department of Medical Sciences, Clinical Chemistry, Uppsala University, Sweden
| | - Robert F Storey
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, UK
| | - Lars Wallentin
- Department of Medical Sciences, Cardiology Uppsala University, Sweden.,Uppsala Clinical Research Center, Uppsala University, Sweden
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45
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Ristagno G, Fumagalli F, Bottazzi B, Mantovani A, Olivari D, Novelli D, Latini R. Pentraxin 3 in Cardiovascular Disease. Front Immunol 2019; 10:823. [PMID: 31057548 PMCID: PMC6481278 DOI: 10.3389/fimmu.2019.00823] [Citation(s) in RCA: 119] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 03/28/2019] [Indexed: 12/30/2022] Open
Abstract
The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The prototype of the pentraxin family is C reactive protein (CRP), a widely-used biomarker in human pathologies with an inflammatory or infectious origin. Data so far describe PTX3 as a multifunctional protein acting as a functional ancestor of antibodies and playing a regulatory role in inflammation. Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and inflammation is crucial in promoting it. Data from animal models indicate that PTX3 can have cardioprotective and atheroprotective roles regulating inflammation. PTX3 has been investigated in several clinical settings as possible biomarker of CVD. Data collected so far indicate that PTX3 plasma levels rise rapidly in acute myocardial infarction, heart failure and cardiac arrest, reflecting the extent of tissue damage and predicting the risk of mortality.
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Affiliation(s)
- Giuseppe Ristagno
- Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy
| | - Francesca Fumagalli
- Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy
| | | | - Alberto Mantovani
- Humanitas Clinical and Research Center-IRCCS, Milan, Italy.,Humanitas University, Milan, Italy.,The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Davide Olivari
- Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy
| | - Deborah Novelli
- Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy
| | - Roberto Latini
- Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy
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46
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Doni A, Stravalaci M, Inforzato A, Magrini E, Mantovani A, Garlanda C, Bottazzi B. The Long Pentraxin PTX3 as a Link Between Innate Immunity, Tissue Remodeling, and Cancer. Front Immunol 2019; 10:712. [PMID: 31019517 PMCID: PMC6459138 DOI: 10.3389/fimmu.2019.00712] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 03/15/2019] [Indexed: 12/20/2022] Open
Abstract
The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation. The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing defense against infectious agents, plays several functions in tissue repair and regulation of cancer-related inflammation. Characterization of the PTX3 molecular structure and biochemical properties, and insights into its interactome and multiple roles in tissue damage and remodeling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.
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Affiliation(s)
- Andrea Doni
- Humanitas Clinical and Research Institute-IRCCS, Milan, Italy
| | - Matteo Stravalaci
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Antonio Inforzato
- Humanitas Clinical and Research Institute-IRCCS, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Elena Magrini
- Humanitas Clinical and Research Institute-IRCCS, Milan, Italy
| | - Alberto Mantovani
- Humanitas Clinical and Research Institute-IRCCS, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy.,The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom
| | - Cecilia Garlanda
- Humanitas Clinical and Research Institute-IRCCS, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Milan, Italy
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47
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Pentraxin 3 Detects Clinically Significant Fibrosis in Patients with Chronic Viral Hepatitis C. BIOMED RESEARCH INTERNATIONAL 2019; 2019:2639248. [PMID: 31061822 PMCID: PMC6466943 DOI: 10.1155/2019/2639248] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/21/2019] [Accepted: 03/11/2019] [Indexed: 02/07/2023]
Abstract
Pentraxin 3 (PTX3) plays a pathogenic role in experimental models of chronic liver injury and contributes to the progression of fibrosis. The detection of advanced fibrosis (METAVIR F≥3) is important to identify patients who are in urgent need of antiviral treatments versus those whose treatment could be deferred (F≥2). The aim was to assess the diagnostic value of PTX3 as a potential biomarker for clinically significant and advanced fibrosis. PTX3 associations with biochemical and histological parameters of inflammatory activity and fibrosis were investigated in 138 patients with chronic viral hepatitis C (HCV) before antiviral treatment. METAVIR histological scores of activity and fibrosis were obtained. PTX3 was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of serum PTX3 levels was compared to that of other fibrosis markers, including transforming growth factor‐β1 (TGF-β1), hyaluronic acid (HA), aspartate transaminase to platelet ratio index (APRI), fibrosis score based on four factors (FIB4), gamma-glutamyltranspeptidase to platelet ratio (GPR), and the liver stiffness measurement (LSM) by transient elastography (FibroScan®). In HCV patients the PTX3 level increased in parallel with the METAVIR histological score of activity, being independently associated with the METAVIR fibrosis score (P < 0.001). Using the receiver operating characteristics analysis, the best marker for detecting F≥2 and F≥3 was PTX3 with AUC = 0.802 and AUC = 0.867, respectively. The area under the curve of PTX3 for predicting significant fibrosis (F≥2) was significantly greater than those for the GPR ratio (AUC = 0.648) and FIB-4 score (AUC = 0.770) and similar to that for APRI index (AUC = 0.831). PTX3 provided clinically relevant diagnostic accuracy as a single marker of significant fibrosis.
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48
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Bonacina F, Moregola A, Porte R, Baragetti A, Bonavita E, Salatin A, Grigore L, Pellegatta F, Molgora M, Sironi M, Barbati E, Mantovani A, Bottazzi B, Catapano AL, Garlanda C, Norata GD. Pentraxin 3 deficiency protects from the metabolic inflammation associated to diet-induced obesity. Cardiovasc Res 2019; 115:1861-1872. [DOI: 10.1093/cvr/cvz068] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 01/23/2019] [Accepted: 03/11/2019] [Indexed: 01/18/2023] Open
Abstract
Abstract
Aims
Low-grade chronic inflammation characterizes obesity and metabolic syndrome. Here, we aim at investigating the impact of the acute-phase protein long pentraxin 3 (PTX3) on the immune-inflammatory response occurring during diet-induced obesity.
Methods and results
PTX3 deficiency in mice fed a high-fat diet for 20 weeks protects from weight gain and adipose tissue deposition in visceral and subcutaneous depots. This effect is not related to changes in glucose homeostasis and lipid metabolism but is associated with an improved immune cell phenotype in the adipose tissue of Ptx3 deficient animals, which is characterized by M2-macrophages polarization and increased angiogenesis. These findings are recapitulated in humans where carriers of a PTX3 haplotype (PTX3 h2/h2 haplotype), resulting in lower PTX3 plasma levels, presented with a reduced prevalence of obesity and decreased abdominal adiposity compared with non-carriers.
Conclusion
Our results support a critical role for PTX3 in the onset of obesity by promoting inflammation and limiting adipose tissue vascularization and delineate PTX3 targeting as a valuable strategy for the treatment of adipose tissue-associated inflammatory response.
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Affiliation(s)
- Fabrizia Bonacina
- Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy
| | - Annalisa Moregola
- Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy
| | - Rémi Porte
- IRCC Humanitas Clinical and Research Center, Rozzano, Italy
| | - Andrea Baragetti
- Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy
- Centro SISA per lo Studio dell’Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy
| | - Eduardo Bonavita
- Cancer Inflammation and Immunity Group, CRUK Manchester Institute, The University of Manchester, Manchester, UK
| | - Alice Salatin
- Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy
| | - Liliana Grigore
- Centro SISA per lo Studio dell’Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy
- IRCSS Multimedica, Milan, Italy
| | - Fabio Pellegatta
- Centro SISA per lo Studio dell’Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy
- IRCSS Multimedica, Milan, Italy
| | | | - Marina Sironi
- IRCC Humanitas Clinical and Research Center, Rozzano, Italy
| | - Elisa Barbati
- IRCC Humanitas Clinical and Research Center, Rozzano, Italy
| | - Alberto Mantovani
- IRCC Humanitas Clinical and Research Center, Rozzano, Italy
- Humanitas University Rozzano, Italy
| | | | - Alberico Luigi Catapano
- Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy
- IRCSS Multimedica, Milan, Italy
| | - Cecilia Garlanda
- IRCC Humanitas Clinical and Research Center, Rozzano, Italy
- Humanitas University Rozzano, Italy
| | - Giuseppe Danilo Norata
- Department of Excellence of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, Italy
- Centro SISA per lo Studio dell’Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy
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49
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Lee R, Ahn HR, Shin MH, Kim HN, Lee YH, Choi SW, Kweon SS. Association of Plasma Pentraxin-3 Level with Lipid Levels and Cardiovascular Risk Factors in People with No History of Lipid-Lowering Medication: the Dong-gu Study. J Atheroscler Thromb 2019; 26:738-745. [PMID: 30674758 PMCID: PMC6711843 DOI: 10.5551/jat.47167] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Aim: To elucidate the role of pentraxin-3 (PTX3) in atherosclerosis, we evaluated lipid and cardiovascular risk profiles according to the plasma PTX3 levels in subjects from the general population. Methods: A sub-cohort of 2,000 subjects was randomly sampled from a Korean community-based cohort study. After excluding those with a medication history for dyslipidemia, 1,747 subjects (902 men and 845 women) were included in the final analyses. Linear and logistic regressions with adjustment for appropriate variables were performed. Results: The PTX3 level was positively associated with the high-density lipoprotein cholesterol (HDL-C) level and negatively associated with the log-transformed triglyceride (TG) level, total cholesterol/HDL-C ratio, and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (p<0.05). Subjects with the highest PTX3 levels (≥ 1.17 ng/dl) exhibited a lower risk of metabolic syndrome (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.57–0.94), overweight/obesity (OR 0.65, 95% CI 0.50–0.83), increased TG level (OR 0.66, 95% CI 0.51–0.86), and increased HDL-C level (OR 0.67, 95% CI 0.51–0.88) compared to those with the lowest PTX3 level (<0.7 ng/dl). Conclusion: The circulating PTX3 level was inversely associated with metabolic syndrome, overweight/obesity, and parameters of dyslipidemia, suggesting a cardioprotective role of PTX3 in atherosclerosis.
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Affiliation(s)
- Ran Lee
- Department of Preventive Medicine, Chonnam National University Medical School
| | | | - Min-Ho Shin
- Department of Preventive Medicine, Chonnam National University Medical School
| | - Hee-Nam Kim
- Department of Preventive Medicine, Chonnam National University Medical School
| | - Young-Hoon Lee
- Department of Preventive Medicine & Institute of Wonkwang Medical Science, Wonkwang University College of Medicine
| | - Seong-Woo Choi
- Department of Preventive Medicine, Chosun University Medical School
| | - Sun-Seog Kweon
- Department of Preventive Medicine, Chonnam National University Medical School.,Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital
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50
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DUSP1 Is a Potential Marker of Chronic Inflammation in Arabs with Cardiovascular Diseases. DISEASE MARKERS 2019; 2018:9529621. [PMID: 30647800 PMCID: PMC6311887 DOI: 10.1155/2018/9529621] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 12/03/2018] [Indexed: 11/17/2022]
Abstract
Background Cardiovascular disease (CVD) risks persist in patients despite the use of conventional treatments. This might be due to chronic inflammation as reflected in epidemiological studies associating circulating low-grade inflammatory markers with CVD recurrent events. Here, we explored this potential link by assessing plasma dual-specificity phosphatase 1 (DUSP1) levels and comparing them to high-sensitivity CRP (hsCRP) and oxidized low-density lipoprotein (oxLDL) levels and their associations to conventional CVD risk factors in confirmed CVD patients. Methods Human adults with reported CVD (n = 207) and controls (n = 70) living in Kuwait were used in this study. Anthropometric and classical biochemical parameters were determined. Plasma levels of DUSP1, oxLDL, and hsCRP were measured using human enzyme-linked immunosorbent assay kits. Results DUSP1 and hsCRP plasma levels and their least square means were higher in CVD cases, while oxLDL plasma levels were lower (p < 0.05). Multivariate logistic regression analysis showed that DUSP1 and hsCRP are independently associated with CVD in the studied population, as reflected by 2-fold and 1.5-fold increased risks with increased levels of DUSP1 and hsCRP, respectively. In our study, DUSP1 levels were found to be associated with CVD despite statin treatment and diabetes status (p < 0.05), whereas hsCRP mainly correlated with obesity markers. Conclusions Circulating DUSP1 might be a predictor of chronic subclinical inflammation and residual risk in CVD patients, whereas our data suggest that the association between hsCRP and CVD is largely accounted for adiposity risk factors.
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