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1
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Tang L, Sun M, Chen J, Dai Q, Xue S, Liu C, Zhang M. Peptide-functionalized nanocapsules for targeted inhibition of β2-microglobulin amyloid aggregation. J Mater Chem B 2025; 13:3319-3324. [PMID: 39928035 DOI: 10.1039/d4tb01347f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2025]
Abstract
Dialysis-related amyloidosis (DRA) is a severe complication in patients undergoing long-term dialysis, primarily driven by the deposition of β2-microglobulin (β2m) amyloid fibrils. The effective sequestration and removal of β2m from the bloodstream represent key therapeutic strategies for managing DRA. In this study, we developed a β2m-binding peptide (KDWSFYILAHTEF, denoted as CF)-functionalized nanocomposite (NC-CF), consisting of a protein nanocapsule surface modified with CF peptides to enable specific β2m binding. NC-CF effectively modulates β2m aggregation, transforming slender fibrils into larger clumps while providing steric hindrance to prevent further aggregation. With a high adsorption capacity, 1 μg of NC-CF can adsorb approximately 1 μg of β2m during dialysis, highlighting its potential as an efficient adsorbent for in vitro β2m removal. Furthermore, NC-CF exhibits excellent biocompatibility and significantly mitigates β2m aggregate-induced cytotoxicity, achieving a cell protection rate exceeding 70%. These findings suggest that NC-CF holds great promise as a cytoprotective agent and a nanoinhibitor of β2m aggregation in vivo. Overall, NC-CF offers a novel and effective approach for alleviating DRA by simultaneously removing β2m and safeguarding cells against amyloid-induced toxicity.
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Affiliation(s)
- Lin Tang
- Department of Medical Imaging, Qilu Medical University, 255100, P. R. China
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China
| | - Miao Sun
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
| | - Junnan Chen
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China
| | - Qiong Dai
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
| | - Song Xue
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
| | - Chaoyong Liu
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
| | - Ming Zhang
- Department of Pathology, Peking University International Hospital, Beijing 102206, P. R. China.
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2
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Kampmann JD, Hunderup MM, Petersen ERB, Andersen V, Skovsted TA. High-sensitive troponin T, suPAR and Beta-2-microglobulin changes in concentration during hemodialysis. Scand J Clin Lab Invest 2024; 84:362-368. [PMID: 39180468 DOI: 10.1080/00365513.2024.2394794] [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: 08/21/2023] [Revised: 05/24/2024] [Accepted: 08/10/2024] [Indexed: 08/26/2024]
Abstract
Hemodialysis (HD) patients are at high risk of cardiovascular disease and death. Reliable biomarkers for risk stratification and detection of acute myocardial infarction (AMI) are therefore pivotal. Cardiac troponins (cTn) are the preferred biomarkers for AMI. It remains unclear, if cTn concentrations changes as a consequence of HD treatment itself during dialysis. In this study, cTn was compared with soluble urokinase plasminogen activator receptor (suPAR) and Beta-2-microglobulin (B2M). We performed a prospective study including 17 HD patients measuring high-sensitive cardiac troponin t (hs-cTnT), suPAR and B2M before and after a dialysis session and verified the results in a random subgroup of eight patients from the group by repeating their measurements before and after a dialysis session 15 weeks later. Biomarker concentrations after dialysis were adjusted according to hemodilution or concentration according to the hemoglobin concentration. The average hs-cTnT concentration decreased significantly by -9.9% after dialysis (95% CI: -13.6% to -6.2%). The average (paired) difference were - 6.7 ng/L (p = 0.0104) after dialysis comparing 25 HD treatment occasions. SuPAR was not significantly influenced by dialysis. B2M decreased by -58% after HD as an expected result from the molecular size of the biomarker. The hs-cTnT in average decreased by -9.9% after dialysis. This is a diagnostic challenge since the current guidelines suggest a 20% change in hs-cTnT in patients with acute myocardial infarction. Larger prospective studies investigating the different factors influencing hs-cTnT after HD are warranted. Adjusting biomarker concentrations according to hemodilution or concentration using the hemoglobin concentration, should be considered in future studies to determine more exact changes in concentrations of cTnT and other relevant biomarkers.
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Affiliation(s)
- Jan D Kampmann
- Department of Internal Medicine, University Hospital of Southern Denmark, Sønderborg, Denmark
| | - Michael M Hunderup
- Department of Blood Test, Biochemistry and Immunology, University Hospital of Southern Denmark, Sønderborg, Denmark
| | - Eva R Brix Petersen
- Department of Blood Test, Biochemistry and Immunology, University Hospital of Southern Denmark, Sønderborg, Denmark
- Department of Biochemistry, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark
| | - Vivi Andersen
- Department of Internal Medicine, University Hospital of Southern Denmark, Sønderborg, Denmark
| | - Thor A Skovsted
- Department of Blood Test, Biochemistry and Immunology, University Hospital of Southern Denmark, Sønderborg, Denmark
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3
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Yu S, Yin P, Li X, Xiao J, Zhang H, Zhou L, Tian Y. Association of high serum β2-microglobulin levels with poor functional outcomes in patients with acute ischemic stroke: A cohort study. Medicine (Baltimore) 2024; 103:e39525. [PMID: 39213200 PMCID: PMC11365628 DOI: 10.1097/md.0000000000039525] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/21/2024] [Accepted: 08/09/2024] [Indexed: 09/04/2024] Open
Abstract
We evaluated the association between serum β2-microglobulin (β2M) levels and prognosis in patients with acute ischemic stroke (AIS) and determined whether the association was affected by any clinical variables. This prospective study included 533 patients with AIS who were admitted to the Hospital of Nanhua Affiliated with the University of South China for treatment from June 1, 2021, to July 31, 2022. Using multiple regression modeling, the association between serum β2M levels and poor functional outcomes-which were classified as being modified Rankin Scale scores of 3 to 6 (composite score of death and major disability), 3 to 5 (major disability), and 6 (death)-were assessed 3 months after stroke onset. At the 3-month follow-up assessment, 209 (47.39%) participants had poor functional outcomes: major disabilities in 150 (34.01%) cases and deaths in 59 (13.38%). After adjusting for important covariates, the group with serum β2M levels in the highest quartile had the highest proportion of individuals with modified Rankin Scale scores of 3 to 6 (odds ratio [OR], 3.54; 95% confidence interval [CI], 1.35-9.33), 3 to 5 (OR, 2.95; 95% CI, 1.21-7.16), or 6 (OR, 1.02; 95% CI, 0.29-3.64) compared with the group having serum β2M levels in the lowest quartiles. The risk prediction for the combined outcome of death and major disability improved after incorporating β2M levels into models that included conventional risk factors. Subgroup analysis revealed a significant impact on the association between serum β2M levels and poor functional outcomes only in patients with AIS whose time from onset to hospitalization was <12 hours (P for interaction < .05). Elevated serum β2M levels were associated with poor functional outcomes in patients with AIS, possibly affected by the time from onset to hospitalization.
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Affiliation(s)
- Shan Yu
- Department of Clinical Laboratory, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Peng Yin
- Department of Information Statistics, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Xiujuan Li
- Department of Clinical Laboratory, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jian Xiao
- Department of Clinical Laboratory, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Hao Zhang
- Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Liangqi Zhou
- Department of Neurology, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Ying Tian
- Department of Clinical Research, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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4
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Zhang Y, Peng G, Leng W, Li Y, Li H, Zhou L, Ge L, Shao J, Li X, Long M. Association between serum β2-microglobulin and left ventricular hypertrophy in patients with type 2 diabetes mellitus: A cross-sectional study. J Diabetes 2024; 16:e13599. [PMID: 39155680 PMCID: PMC11331034 DOI: 10.1111/1753-0407.13599] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/01/2024] [Accepted: 06/10/2024] [Indexed: 08/20/2024] Open
Abstract
BACKGROUND Beta 2-microglobulin (β2-MG) is a component of the class I major histocompatibility complex (MHCI) and has recently been reported to be involved in type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, the association of β2-MG with left ventricular hypertrophy (LVH) in T2DM patients remains unknown. This study aims to investigate the correlation between serum β2-MG and LVH in T2DM patients. METHODS The retrospective analysis included 4602 eligible T2DM patients, divided into LVH and non-LVH groups based on echocardiography results. Serum β2-MG levels were measured, and participants were categorized into four groups (Q1-Q4) by their serum β2-MG quartile. The relationship of serum β2-MG level with LVH was evaluated using logistic regression, restricted cubic spline (RCS), subgroup analysis, and machine learning. RESULTS The prevalence of LVH in T2DM patients was 31.12%. Each standard deviation increase in serum β2-MG level corresponded to a 1.17-fold increase in the prevalence of LVH [OR = 1.17, (95% CI: 1.05-1.31); p = 0.006]. When considering β2-MG as a categorical variable (quartile), Q3 [OR = 1.36, (95% CI: 1.09-1.69); p = 0.007] and Q4 [OR = 1.77, (95% CI: 1.36-2.31); p < 0.001] had a significantly higher prevalence of LVH than Q1. RCS analysis found a nonlinear association between β2-MG and LVH prevalence (p for nonlinearity <0.05). Additionally, machine learning results confirmed the importance of β2-MG for LVH in T2DM patients. CONCLUSION Elevated serum β2-MG levels were likely to be associated with an increased prevalence of LVH in T2DM patients, suggesting its potential role in LVH development.
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Affiliation(s)
- Yuling Zhang
- Department of EndocrinologySouthwest Hospital, Army Medical University (Third Military Medical University)ChongqingChina
| | - Guiliang Peng
- Department of EndocrinologySouthwest Hospital, Army Medical University (Third Military Medical University)ChongqingChina
| | - Weiling Leng
- Department of EndocrinologySouthwest Hospital, Army Medical University (Third Military Medical University)ChongqingChina
| | - Ying Li
- Center for Medical Big Data and Artificial Intelligence, Southwest Hospital, Army Medical University (Third Military Medical University)ChongqingChina
| | - Haiyan Li
- Department of UltrasonographyChenjiaqiao HospitalChongqingChina
| | - Ling Zhou
- Department of EndocrinologySouthwest Hospital, Army Medical University (Third Military Medical University)ChongqingChina
| | - Lichao Ge
- Department of EndocrinologyJinling Hospital, Nanjing Medical UniversityNanjingChina
| | - Jiaqing Shao
- Department of EndocrinologyJinling Hospital, Nanjing Medical UniversityNanjingChina
- Department of EndocrinologyJinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
- Department of EndocrinologyJinling Hospital, School of Medicine, Southeast UniversityNanjingChina
| | - Xing Li
- Department of EndocrinologyJinling Hospital, Nanjing Medical UniversityNanjingChina
- Department of EndocrinologyJinling Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
- Department of EndocrinologyJinling Hospital, School of Medicine, Southeast UniversityNanjingChina
| | - Min Long
- Department of EndocrinologySouthwest Hospital, Army Medical University (Third Military Medical University)ChongqingChina
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5
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Jheng JR, DesJardin JT, Chen YY, Huot JR, Bai Y, Cook T, Hibbard LM, Rupp JM, Fisher A, Zhang Y, Duarte JD, Desai AA, Machado RF, Simon MA, Lai YC. Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction. Arterioscler Thromb Vasc Biol 2024; 44:1570-1583. [PMID: 38813697 PMCID: PMC11208054 DOI: 10.1161/atvbaha.123.320270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 05/13/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear. METHODS We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples. RESULTS Plasma proteomics identified high protein abundance levels of B2M (β2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, B2m deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF. CONCLUSIONS Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.
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MESH Headings
- Adult
- Aged
- Animals
- Humans
- Male
- Mice
- Middle Aged
- beta 2-Microglobulin/genetics
- beta 2-Microglobulin/blood
- beta 2-Microglobulin/metabolism
- Biomarkers/blood
- Case-Control Studies
- Cell Movement
- Cell Proliferation
- Cells, Cultured
- Disease Models, Animal
- Endothelial Cells/metabolism
- Endothelial Cells/pathology
- Heart Failure/physiopathology
- Heart Failure/metabolism
- Heart Failure/blood
- Heart Failure/genetics
- Hypertension, Pulmonary/physiopathology
- Hypertension, Pulmonary/metabolism
- Hypertension, Pulmonary/blood
- Hypertension, Pulmonary/etiology
- Hypertension, Pulmonary/genetics
- Mice, Inbred C57BL
- Mice, Knockout
- Muscle, Skeletal/metabolism
- Proteomics/methods
- Pulmonary Artery/physiopathology
- Pulmonary Artery/metabolism
- Sirtuin 3/genetics
- Sirtuin 3/metabolism
- Stroke Volume
- Vascular Remodeling
- Ventricular Function, Left
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Affiliation(s)
- Jia-Rong Jheng
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine (J.-R.J., Y.B., T.C., A.F., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
| | | | - Yi-Yun Chen
- Academia Sinica Common Mass Spectrometry Facilities for Proteomics and Protein Modification Analysis, Nankang, Taipei, Taiwan (Y.-Y.C.)
- Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei, Taiwan (Y.-Y.C.)
| | - Joshua R. Huot
- Department of Anatomy, Cell Biology and Physiology (J.R.H., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
| | - Yang Bai
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine (J.-R.J., Y.B., T.C., A.F., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
- Department of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang (Y.B.)
| | - Todd Cook
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine (J.-R.J., Y.B., T.C., A.F., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
| | - Lainey M. Hibbard
- Department of Medical and Molecular Genetics (L.M.H., J.M.R.), Indiana University School of Medicine, Indianapolis
| | - Jennifer M. Rupp
- Department of Medical and Molecular Genetics (L.M.H., J.M.R.), Indiana University School of Medicine, Indianapolis
| | - Amanda Fisher
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine (J.-R.J., Y.B., T.C., A.F., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
| | - Yingze Zhang
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, PA (Y.Z.)
| | - Julio D. Duarte
- Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville (J.D.D.)
| | - Ankit A. Desai
- Krannert Cardiovascular Research Center (A.A.D.), Indiana University School of Medicine, Indianapolis
| | - Roberto F. Machado
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine (J.-R.J., Y.B., T.C., A.F., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
- Department of Anatomy, Cell Biology and Physiology (J.R.H., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
| | - Marc A. Simon
- Division of Cardiology, University of California, San Francisco (J.T.D.J., M.A.S.)
| | - Yen-Chun Lai
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine (J.-R.J., Y.B., T.C., A.F., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
- Department of Anatomy, Cell Biology and Physiology (J.R.H., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis
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Krittanawong C, Escobar J, Virk HUH, Alam M, Virani S, Lavie CJ, Narayan KMV, Sharma R. Lifestyle Approach and Medical Therapy of Lower Extremity Peripheral Artery Disease. Am J Med 2024; 137:202-209. [PMID: 37980970 DOI: 10.1016/j.amjmed.2023.10.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 11/21/2023]
Abstract
Lower extremity peripheral artery disease (PAD) is common among patients with several risk factors, such as elderly, smoking, hypertension, and diabetes mellitus. Notably, PAD is associated with a higher risk of cardiovascular complications. Non-invasive interventions are beneficial to improve morbidity and mortality among patients with PAD. Traditional risk factors like smoking, diabetes mellitus, hypertension, and dyslipidemia play a significant role in the development of PAD. Still, additional factors such as mental health, glycemic control, diet, exercise, obesity management, lipid-lowering therapy, and antiplatelet therapy have emerged as important considerations. Managing these factors can help improve outcomes and reduce complications in PAD patients. Antiplatelet therapy with aspirin or clopidogrel is recommended in PAD patients, with clopidogrel showing more significant benefits in symptomatic PAD individuals. Managing several risk factors is crucial for improving outcomes and reducing complications in patients with PAD. Further research is also needed to explore the potential benefits of novel therapies. Ultimately, a comprehensive approach to PAD management is essential for improving morbidity and mortality among patients with this condition.
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Affiliation(s)
| | - Johao Escobar
- Division of Cardiology, Harlem Cardiology, New York, NY
| | - Hafeez Ul Hassan Virk
- Harrington Heart & Vascular Institute, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | | | - Salim Virani
- Section of Cardiology, Baylor College of Medicine, Houston, Texas; The Aga Khan University, Karachi, Pakistan; Baylor College of Medicine, Houston, Texas
| | - Carl J Lavie
- John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, La
| | - K M Venkat Narayan
- Emory Global Diabetes Research Center, Woodruff Health Sciences Center and Emory University, Atlanta, Ga
| | - Raman Sharma
- Department of Medicine/Cardiology, The Zena and Michael A. Wiener Cardiovascular Institute and the Marie-Josée Henry R. Kravis Cardiovascular Health Center, Icahn School of Medicine at the Mount Sinai Hospital, Mount Sinai Heart, New York, NY
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7
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Lan T, Zeng Q, Fan Y, Liu T, Yao P, Liang Z, Dang X, Zhu H, Li Y, Jiang W, Lu W. Proteomics Analysis of Serum Reveals Potential Biomarkers for Heart Failure Patients with Phlegm-Blood Stasis Syndrome. J Proteome Res 2024; 23:226-237. [PMID: 38048169 DOI: 10.1021/acs.jproteome.3c00537] [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] [Indexed: 12/06/2023]
Abstract
Heart failure (HF), a complex clinical syndrome, has become a global burden on health and economics around the world. Phlegm-blood stasis syndrome, one of the Traditional Chinese Medicine (TCM) syndrome differentiation, is the core pathogenesis dynamically throughout the occurrence, development, and prognosis of HF. Biomarkers having high sensitivity and specificity are highly demanded to facilitate the accurate differentiation of HF patients with phlegm-blood stasis syndrome. In the present study, serum samples were collected from 20 healthy controls and 40 HF patients (20 with and 20 without phlegm-blood stasis syndrome). We implemented data-independent acquisition mass spectrometry (DIA-MS) for discovery and parallel reaction monitoring (PRM) for validation of biomarkers for heart failure with phlegm-blood stasis syndrome. A total of 84 different proteins were found in the HF with phlegm-blood stasis syndrome (HF-TY) group compared with healthy controls. 37 candidate proteins were selected for the PRM assay, and five validated proteins with high sensitivity and specificity, including insulin-like growth factor-binding protein 4 (IGFBP4), β-2-microglobulin (B2M), dystroglycan (DAG1), immunoglobulin J chain (JCHAIN), and kallikrein B1 (KLKB1), were considered potential biomarkers for heart failure patients with phlegm-blood stasis syndrome. Newly identified biomarkers might provide insights into the diagnosis and treatment of HF with TCM syndrome differentiation.
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Affiliation(s)
- Taohua Lan
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510020, China
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou 510020, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Qiaohuang Zeng
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Yunxiang Fan
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Tong Liu
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Ping Yao
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Zhaoying Liang
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Xiaojing Dang
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Huiying Zhu
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Yanfen Li
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Wei Jiang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510020, China
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou 510020, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
| | - Weihui Lu
- Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou 510020, China
- Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510020, China
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510020, P. R. China
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8
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Leeper NJ, Adkar SS. A Glimpse Into the Black Box: Using Machine Learning to Prioritize Predictors of Vascular Disease. JACC. ADVANCES 2023; 2:100563. [PMID: 38939483 PMCID: PMC11198632 DOI: 10.1016/j.jacadv.2023.100563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
Affiliation(s)
- Nicholas J. Leeper
- Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
- Stanford Cardiovascular Institute, Stanford, California, USA
| | - Shaunak S. Adkar
- Division of Vascular Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, USA
- Stanford Cardiovascular Institute, Stanford, California, USA
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9
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Jin YX, Zhang S, Xiao J, Wang ZH, Dong C, You LL, Kuai TT, Zhang Y, Liu SX. Association between serum β 2-microglobulin levels and the risk of all-cause and cardiovascular disease mortality in chinese patients undergoing maintenance hemodialysis. BMC Nephrol 2023; 24:170. [PMID: 37312042 DOI: 10.1186/s12882-023-03191-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 04/28/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND The association between serum β2-microglobulin (β2M) levels and the risk of all-cause and cardiovascular disease (CVD) mortality and the incidence of cardiovascular events (CVEs) in patients undergoing maintenance hemodialysis (MHD) is inconclusive. Furthermore, no study has been performed in China on the significance of serum β2M levels in MHD patients. Therefore, this study investigated the aforementioned association in MHD patients. METHODS In this prospective cohort study, 521 MHD patients were followed at Dalian Municipal Central Hospital affiliated with Dalian University of Technology from December 2019 to December 2021. The serum β2M levels were categorized into three tertiles, and the lowest tertile served as the reference group. Survival curves were calculated by the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. Sensitivity analysis was performed by excluding patients with CVD at baseline. RESULTS During the follow-up period of 21.4 ± 6.3 months, there were 106 all-cause deaths, of which 68 were caused by CVD. When excluding CVD patients at baseline, there were 66 incident CVEs. Kaplan-Meier analysis revealed that the risk of all-cause and CVD mortality in the highest tertile of serum β2M levels was significantly higher than that in the lowest tertile (P < 0.05), but not for the CVEs (P > 0.05). After adjusting for potential confounders, serum β2M levels were positively associated with the risk of all-cause (HR = 2.24, 95% CI = 1.21-4.17) and CVD (HR = 2.54, 95% CI = 1.19-5.43) mortality, and a linear trend was evident (P < 0.05). Besides, the results of sensitivity analysis were consistent with the main findings. However, we didn't observed the significant association between serum β2M levels and CVEs (P > 0.05). CONCLUSION The serum β2M level may be a significant predictor of the risk of all-cause and CVD mortality in MHD patients. Further studies are needed to confirm this finding.
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Affiliation(s)
- Yu-Xin Jin
- Graduate School, Dalian Medical University, Dalian, China
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Shuang Zhang
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Jia Xiao
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Zhi-Hong Wang
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Cui Dong
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Lian-Lian You
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Ting-Ting Kuai
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Yu Zhang
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China
| | - Shu-Xin Liu
- Dalian Key Laboratory of Intelligent Blood Purifcation, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, Dalian, China.
- Department of Nephrology, Dalian Municipal Central Hospital affiliated with Dalian University of Technology, No.826, Xinan Road Dalian, 116033, Liaoning, P. R. China.
- School of Clinical Medicine, Faculty of Medicine, Dalian University of Technology, Dalian, China.
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10
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Donghia R, Schiano Di Cola R, Cesaro F, Vitale A, Lippolis G, Lisco T, Isernia R, De Pergola G, De Nucci S, Rinaldi R, Liso M, Giardiello C. Gender and Liver Steatosis Discriminate Different Physiological Patterns in Obese Patients Undergoing Bariatric Surgery: Obesity Center Cohort. Nutrients 2023; 15:nu15102381. [PMID: 37242264 DOI: 10.3390/nu15102381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/20/2023] [Accepted: 03/20/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Obesity is a major public health problem worldwide. Bariatric surgery can reduce body weight, and it is one of the better ways to improve metabolic disease and lifestyle. The aim of this study was to explore a new cohort of patients with obesity and evaluate the gender differences and the steatosis status within the gender group. METHODS A cohort of 250 adult obese patients with BMI ≥ 30 and age >18 years, eligible for gastric bariatric surgery at Pineta Grande Hospital, Castel Volturno (Italy) was studied. RESULTS The prevalence in women was higher (72.40%) than men (27.60%). Overall, results indicated many statistically significant gender differences in hematological and clinical parameters. Analysis of the subcohorts based on the severity of steatosis revealed differences of this condition between the genders. Steatosis was more prevalent in the male subcohort, but female patients revealed greater within-group differences. CONCLUSIONS Many differences were found not only in the total cohort but also between the gender subcohorts, both in the presence and absence of steatosis. We can conclude that the pathophysiological, genetic, and hormonal patterns affecting these patients delineate different individual profiles.
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Affiliation(s)
- Rossella Donghia
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | | | | | - Andrea Vitale
- Pineta Grande Hospital, 81030 Castel Volturno, Italy
| | - Giuseppe Lippolis
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | - Teresa Lisco
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | - Roberta Isernia
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | - Giovanni De Pergola
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | - Sara De Nucci
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | - Roberta Rinaldi
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | - Marina Liso
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
| | - Cristiano Giardiello
- National Institute of Gastroenterology-IRCCS "Saverio de Bellis", 70013 Castellana Grotte, Italy
- Pineta Grande Hospital, 81030 Castel Volturno, Italy
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11
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Fang H, Zhang Q, Jin L. Association of beta-2-microglobulin with cardiovascular and all-cause mortality in the general and non-CKD population. Medicine (Baltimore) 2023; 102:e33202. [PMID: 36930114 PMCID: PMC10019200 DOI: 10.1097/md.0000000000033202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 02/15/2023] [Indexed: 03/18/2023] Open
Abstract
β-2 microglobulin, a light chain in the major histocompatibility complex Class 1 molecule, is associated with mortality in dialysis or uremic patients. Current evidence on the relationship between beta-2-microglobulin (B2M) and mortality in the general and non-chronic kidney disease (CKD) population are limited and controversial. Data from the nutrition and health examination survey database and the nutrition and health examination survey linked mortality file were used. In total, 10,388 adults who had complete data for B2M were included. Weighted multivariable Cox proportional hazards regression models and regression splines were employed to evaluate the relationship between B2M with mortality. Moreover, subgroup and sensitivity analyses were performed. During a median follow up of 17.9 years (interquartile range 15.2-18.7), 2780 people died, 902 (32%) from cardiovascular disease. Restricted cubic splines showed that B2M is J-shaped nonlinear positively associated with all-cause mortality and cardiovascular disease mortality in the non-CKD and general population. Based on the multivariable adjustment model, the adjusted hazard ratios comparing the highest versus lowest quartile of the distribution of B2M were 2.50 (95% confidence interval: 1.90, 3.28) for all-cause mortality in the general population, 2.58 (95% confidence interval: 1.52, 4.37) for cardiovascular disease mortality in the general population, 2.58 (1.91, 3.49) for all-cause mortality in the non-CKD population and 2.62 (1.52, 4.53) for cardiovascular disease mortality in the non-CKD population. The positive associations between B2M and outcomes remained broadly significant across subgroups and sensitivity analyses. Higher B2M levels were associated with cardiovascular and all-cause mortality in the general and non-CKD population.
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Affiliation(s)
- Hang Fang
- Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Qiankun Zhang
- Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, China
| | - Lie Jin
- Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, China
- Department of Nephrology, Lishui Central Hospital and The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China
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12
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13
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Zamzam A, Syed MH, Rotstein OD, Eikelboom J, Klein DJ, Singh KK, Abdin R, Qadura M. Validating fatty acid binding protein 3 as a diagnostic and prognostic biomarker for peripheral arterial disease: A three-year prospective follow-up study. EClinicalMedicine 2023; 55:101766. [PMID: 36531981 PMCID: PMC9755058 DOI: 10.1016/j.eclinm.2022.101766] [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: 08/25/2022] [Revised: 11/14/2022] [Accepted: 11/15/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Patients with peripheral arterial disease (PAD) often remain undiagnosed and therefore suboptimally managed. Here, we investigated the diagnostic and prognostic potential of fatty acid binding protein 3 (FABP3) in patients with PAD. METHODS In the discovery phase, 374 PAD and 184 non-PAD patients were recruited from vascular surgery ambulatory clinics at St. Michael's Hospital (Toronto, Ontario, Canada) between October 4, 2017 to October 29, 2018. The diagnostic ability of baseline FABP3 level was investigated through receiver operator characteristic (ROC) curves to determine two cutoff points: 1) an exclusionary "rule out" cutoff point, and 2) a confirmatory "rule in" cutoff point. Next, these cutoff points were confirmed in the external validation phase using a separate cohort of 312 patients (180 PAD and 132 non-PAD) recruited from ambulatory vascular surgery clinics at St. Michael's Hospital (Canada) between November 6, 2018-July 30, 2019. Cox regression analyses were used to explore the independent association between FABP3 and major adverse limb events (MALE - defined as need for arterial revascularization or major amputation) and decrease in ankle-brachial index (ABI -defined as drop ≥0.15) during 3 years of follow-up. FINDINGS In the discovery phase, FABP3 levels were significantly elevated in patients with PAD compared to non-PAD patients. ROC analysis demonstrated that FABP3 had an AUC of 0.83 (95% CI: 0.81-0.86, p-value < 0.001). FABP3 exclusionary cutoff was <1.55 ng/ml (sensitivity = 96%; specificity = 40%), whereas FABP3 confirmatory cutoff was >3.55 ng/ml (sensitivity = 43%; specificity = 95%) - values that were confirmed in the external validation phase. Cox regression analysis demonstrated FABP3 to be an independent predictor of increase in MALE [HR = 1.14 (1.03-1.29); p-value = 0.010] and worsening PAD status (drop in ABI >0.15 [HR = 1.11 (1.02-1.19); p-value = 0.009]). INTERPRETATION Our findings suggested that FABP3 levels can be used as both a diagnostic and prognostic biomarker for PAD, and may facilitate risk stratification in select individuals for purposes of vascular evaluation or intensive medical management. FUNDING Funding for this study was provided by the Bill and Vicky Blair Foundation.
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Affiliation(s)
- Abdelrahman Zamzam
- Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada
| | - Muzammil H. Syed
- Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada
| | - Ori D. Rotstein
- Department of Surgery, University of Toronto, Toronto, ON, M5S 1A1, Canada
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada
| | - John Eikelboom
- Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - David J. Klein
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
- Department of Critical Care, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada
| | - Krishna K. Singh
- Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, N6A 5C1, Canada
| | - Rawand Abdin
- Department of Medicine, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Mohammad Qadura
- Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada
- Department of Surgery, University of Toronto, Toronto, ON, M5S 1A1, Canada
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada
- Corresponding author. St. Michael's Hospital, 30 Bond St, 7-076 Bond Wing, Toronto, Ontario, M5B 1W8, Canada.
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14
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Guo ZJ, Xu Q, Bai ZM, Liu Y, Lin Q, Zhao BH, Liu HT. Factors associated with brain white matter damage in type 2 diabetes mellitus: a tract-based spatial statistics study. Acta Radiol 2022; 63:1678-1688. [PMID: 34851138 DOI: 10.1177/02841851211056471] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND The pathogenesis and related factors of central nervous system abnormality in patients with type 2 diabetes mellitus (T2DM) have always been the focus of clinical research. PURPOSE To compare and analyze the area of white matter (WM) damage in patients with T2DM based on their level of hemoglobin A1C (HBA1c) and discuss any related factors. MATERIAL AND METHODS Based on their levels of HBA1c, 87 patients with T2DM were divided into three groups (Group B, C, or D), of which 29 non-diabetic volunteers served as the control group (Group A). DTI data analysis was based on tract-based spatial statistics (TBSS). The obtained parameters were compared among each group and the relevant clinical factors were analyzed. RESULTS For age, sex, mini-mental state examination (MMSE), and Montreal Cognitive Assessment (MoCA) scores, there were no statistically significant differences among groups. For fractional anisotropy (FA) and radial diffusivity (RD) of WM, there were statistically significant differences (P < 0.05, two-tailed, FWE corrected) in the local area of corpus callosum, corona radiate, superior longitudinal fasciculus, etc. Most of these were significantly correlated with body mass index (BMI), left systolic blood pressure (SBP_L), and β2 microglobulin. CONCLUSION Before the cognitive function was obviously impaired, abnormalities of FA and RD had been found in the corpus callosum, corona radiate, and upper fasciculus in patients with T2DM, which suggested that the damage mainly occurred in the myelin sheath of WM and may be related to systemic vascular damage.
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Affiliation(s)
- Zhi-Jun Guo
- Department of Radiology, Huabei Petroleum General Hospital, Renqiu, Hebei, PR China
| | - Qian Xu
- Department of Radiology, Huabei Petroleum General Hospital, Renqiu, Hebei, PR China
| | - Ze-Mei Bai
- Department of medical administration, Huabei Petroleum Health Bureau, Renqiu, Hebei, PR China
| | - Yan Liu
- School of computer science and technology, 538800University of Chinese Academy of Sciences, Beijing, PR China
| | - Qiang Lin
- Department of oncology, Huabei Petroleum General Hospital, Renqiu, Hebei, PR China
| | - Bao-Hong Zhao
- Department of Radiology, Huabei Petroleum General Hospital, Renqiu, Hebei, PR China
| | - Hai-Tao Liu
- Department of respiratory medicine, Huabei Petroleum General Hospital, Renqiu, Hebei, PR China
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15
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Feng J, Yu L, Li H, Wang S. High serum β2‐microglobulin is a significant predictor of mortality in maintenance hemodialysis patients. Semin Dial 2022; 36:247-254. [PMID: 36372394 DOI: 10.1111/sdi.13128] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 07/07/2022] [Accepted: 10/18/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Beta2-microglobulin, a novel marker of kidney function, predicts kidney failure and mortality in the general population. However, few studies have evaluated the association of serum β2-MG level with clinical outcome in maintenance hemodialysis (MHD) patients. METHODS This prospective cohort study enrolled 303 MHD patients to investigate the factors related to β2-MG and its relationship to mortality in MHD patients. Multivariate linear regression analysis was used to examine the factors related to β2-MG level. Multivariable Cox regression was used to calculate the hazard ratios for β2-MG on all-cause and cardiovascular mortality. RESULTS The median value of serum β2-MG was 44.6 mg/L (interquartile range 37.60-50.40 mg/L). During the follow-up period of 24 months, there were 48 all-cause deaths (23.0%), including 36 cardiovascular causes (75.0% of all deaths). Multiple linear regression showed that dialysis duration, serum creatinine, and alkaline phosphatase were independent predictors of serum β2-MG level. Kaplan-Meier analysis revealed that mortality in MHD patients was significantly higher in low albumin patients with β2-MG > 44.6 mg/L. Cox regression analysis showed that β2-MG was a significant predictor of all-cause mortality (HR = 1.122, 95% CI: 1.058-1.190, 𝑃 < 0.001) and cardiovascular mortality (HR = 1.145, 95%CI: 1.065-1.123, P < 0.001) in MHD patients with low albumin level after adjusting for confounding factors. However, our results showed that serum β2-MG was not associated with mortality in MHD patients with normal albumin level. CONCLUSION These results are supportive of the potential role of the serum β2-MG level as a predictor of mortality in MHD patients with low albumin.
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Affiliation(s)
- Jianan Feng
- Department of Nephrology, Beijing Chao‐Yang Hospital Capital Medical University Beijing China
| | - Ling Yu
- Department of Nephrology, Beijing Chao‐Yang Hospital Capital Medical University Beijing China
| | - Han Li
- Department of Nephrology, Beijing Chao‐Yang Hospital Capital Medical University Beijing China
| | - Shixiang Wang
- Department of Nephrology, Beijing Chao‐Yang Hospital Capital Medical University Beijing China
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16
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Vyletelová V, Nováková M, Pašková Ľ. Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies. Pharmaceuticals (Basel) 2022; 15:1278. [PMID: 36297390 PMCID: PMC9611871 DOI: 10.3390/ph15101278] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/03/2022] [Accepted: 10/14/2022] [Indexed: 09/10/2023] Open
Abstract
Chronic inflammatory diseases, such as rheumatoid arthritis, steatohepatitis, periodontitis, chronic kidney disease, and others are associated with an increased risk of atherosclerotic cardiovascular disease, which persists even after accounting for traditional cardiac risk factors. The common factor linking these diseases to accelerated atherosclerosis is chronic systemic low-grade inflammation triggering changes in lipoprotein structure and metabolism. HDL, an independent marker of cardiovascular risk, is a lipoprotein particle with numerous important anti-atherogenic properties. Besides the essential role in reverse cholesterol transport, HDL possesses antioxidative, anti-inflammatory, antiapoptotic, and antithrombotic properties. Inflammation and inflammation-associated pathologies can cause modifications in HDL's proteome and lipidome, transforming HDL from atheroprotective into a pro-atherosclerotic lipoprotein. Therefore, a simple increase in HDL concentration in patients with inflammatory diseases has not led to the desired anti-atherogenic outcome. In this review, the functions of individual protein components of HDL, rendering them either anti-inflammatory or pro-inflammatory are described in detail. Alterations of HDL proteome (such as replacing atheroprotective proteins by pro-inflammatory proteins, or posttranslational modifications) in patients with chronic inflammatory diseases and their impact on cardiovascular health are discussed. Finally, molecular, and clinical aspects of HDL-targeted therapies, including those used in therapeutical practice, drugs in clinical trials, and experimental drugs are comprehensively summarised.
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Affiliation(s)
| | | | - Ľudmila Pašková
- Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 83232 Bratislava, Slovakia
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Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease. Int J Mol Sci 2022; 23:ijms231912054. [PMID: 36233355 PMCID: PMC9569699 DOI: 10.3390/ijms231912054] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 09/26/2022] [Accepted: 10/02/2022] [Indexed: 12/24/2022] Open
Abstract
Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one’s predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options.
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18
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Analysis of the B2M Expression in Colon Adenocarcinoma and Its Correlation with Patient Prognosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:7264503. [PMID: 35982994 PMCID: PMC9381202 DOI: 10.1155/2022/7264503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 06/09/2022] [Indexed: 11/17/2022]
Abstract
Colon adenocarcinoma (COAD) is one of the most common malignant tumors in clinics. It is often found at an advanced stage, with high incidence and poor prognosis; early diagnosis is difficult and treatment methods are limited. In order to find new methods for diagnosis and treatment of COAD, people pay more and more attention to the discovery and functional research of new oncogenes and tumor suppressor genes of COAD. β2-microglobulin (B2M) plays different physiological and pathological roles in tumor cells and nontumor cells. At present, there is no public report on the expression of B2M in COAD. In this study, the expression of B2M mRNA in COAD tissues was compared with that in normal tissues. The relationship between the expression of B2M mRNA and the stage, histological subtype, lymph node metastasis, TP53 mutation, and survival time of COAD was discussed. It was found that B2M is a potential tumor suppressor gene in COAD. The decreased expression of B2M after mutation can cause immune escape of COAD cells, thus affecting the therapeutic effect and prognosis. This study provides a new idea for the prevention and treatment of COAD.
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Sivanathan PC, Ooi KS, Mohammad Haniff MAS, Ahmadipour M, Dee CF, Mokhtar NM, Hamzah AA, Chang EY. Lifting the Veil: Characteristics, Clinical Significance, and Application of β-2-Microglobulin as Biomarkers and Its Detection with Biosensors. ACS Biomater Sci Eng 2022; 8:3142-3161. [PMID: 35848712 DOI: 10.1021/acsbiomaterials.2c00036] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Because β-2-microglobulin (β2M) is a surface protein that is present on most nucleated cells, it plays a key role in the human immune system and the kidney glomeruli to regulate homeostasis. The primary clinical significance of β2M is in dialysis-related amyloidosis, a complication of end-stage renal disease caused by a gradual accumulation of β2M in the blood. Therefore, the function of β2M in kidney-related diseases has been extensively studied to evaluate its glomerular and tubular functions. Because increased β2M shedding due to rapid cell turnover may indicate other underlying medical conditions, the possibility to use β2M as a versatile biomarker rose in prominence across multiple disciplines for various applications. Therefore, this work has reviewed the recent use of β2M to detect various diseases and its progress as a biomarker. While the use of state-of-the-art β2M detection requires sophisticated tools, high maintenance, and labor cost, this work also has reported the use of biosensor to quantify β2M over the past decade. It is hoped that a portable and highly efficient β2M biosensor device will soon be incorporated in point-of-care testing to provide safe, rapid, and reliable test results.
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Affiliation(s)
- P C Sivanathan
- Institute of Microengineering and Nanoelectronics, Universiti Kebangsaan Malaysia, 43600 Bangi, Malaysia
| | - Kai Shen Ooi
- Institute of Microengineering and Nanoelectronics, Universiti Kebangsaan Malaysia, 43600 Bangi, Malaysia.,Department of Paediatrics, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia
| | | | - Mohsen Ahmadipour
- Institute of Microengineering and Nanoelectronics, Universiti Kebangsaan Malaysia, 43600 Bangi, Malaysia
| | - Chang Fu Dee
- Institute of Microengineering and Nanoelectronics, Universiti Kebangsaan Malaysia, 43600 Bangi, Malaysia
| | - Norfilza Mohd Mokhtar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia
| | - Azrul Azlan Hamzah
- Institute of Microengineering and Nanoelectronics, Universiti Kebangsaan Malaysia, 43600 Bangi, Malaysia
| | - Edward Y Chang
- Department of Material Science and Engineering, International College of Semiconductor Technology, National Yang Ming Chiao Tung University, 30010 Hsinchu, Taiwan
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Hu FY, Wu W, Liu Q, Wu J, Guo H, Yang J, Wu Z, Jiang K, Wang G, Qian Y, Ge W, Qun S. β2-Microglobulin is a Novel and Reliable Biomarker for Predicting Ischemic Stroke Recurrence: A Prospective Cohort Study. Front Pharmacol 2022; 13:916769. [PMID: 35784756 PMCID: PMC9247298 DOI: 10.3389/fphar.2022.916769] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 05/05/2022] [Indexed: 11/24/2022] Open
Abstract
Immune and inflammatory mechanisms play key roles in the development and outcome of acute ischemic stroke (AIS). β2-Microglobulin (β2M) is the light chain of major histocompatibility complex-1 (MHC-1), which can directly and quickly reflect the immune and inflammatory state of the body. Previous studies have shown a close relationship between β2M and AIS, but its relationship with the recurrence of AIS has not been reported. This study attempted to explore the relationship between β2M and the recurrence of AIS. A single-center AIS cohort involving 135 patients was followed for approximately 26-46 months. Clinical and laboratory data from the patients were collected when hospitalized. The endpoint was the occurrence of recurrent AIS after patients were discharged. Propensity score matching was used to match cohort groups. Cox regression analysis was used to predict risk factors for recurrent AIS, and receiver operating characteristic curve (ROC) analysis was used to calculate the optimal cutoff value for discriminating recurrence in patients with AIS. The rate of recurrence was 29.6% [95% CI, 21.8%-37.3%] in the follow-up group. Patients with higher levels of serum β2M had a higher risk of AIS recurrence than patients with lower levels of β2M (adjusted hazard ratio, 3.214 [95% CI, 1.557-6.633]; adjusted hazard ratio after matching, 5.831, [95% CI, 2.052-16.572]). A β2M value of 2.31 mg/L was calculated by ROC analysis as the optimal cutoff value for AIS recurrence (area under the curve 0.770, [95% CI, 0.687-0.853]). As a quick responder to the body's immune and inflammatory states, β2M may be a novel and reliable biomarker in predicting AIS recurrence.
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Affiliation(s)
- Fu-yong Hu
- School of Public Health, Bengbu Medical College, Bengbu, China
- Division of Life Sciences and Medicine, The Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Wentao Wu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Qiuwan Liu
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University (No. 2 People’s Hospital of Hefei), Hefei, China
| | - Juncang Wu
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University (No. 2 People’s Hospital of Hefei), Hefei, China
| | - Hualing Guo
- Division of Life Sciences and Medicine, The Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Jing Yang
- Division of Life Sciences and Medicine, The Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Zhuqing Wu
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University (No. 2 People’s Hospital of Hefei), Hefei, China
| | - Ke Jiang
- Division of Life Sciences and Medicine, The Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Guoping Wang
- Division of Life Sciences and Medicine, The Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
| | - Yu Qian
- Department of Neurosurgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wei Ge
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Sen Qun
- Division of Life Sciences and Medicine, The Stroke Center and Department of Neurology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China
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21
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Bonilla DA, Moreno Y, Petro JL, Forero DA, Vargas-Molina S, Odriozola-Martínez A, Orozco CA, Stout JR, Rawson ES, Kreider RB. A Bioinformatics-Assisted Review on Iron Metabolism and Immune System to Identify Potential Biomarkers of Exercise Stress-Induced Immunosuppression. Biomedicines 2022; 10:724. [PMID: 35327526 PMCID: PMC8945881 DOI: 10.3390/biomedicines10030724] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 03/01/2022] [Accepted: 03/09/2022] [Indexed: 02/01/2023] Open
Abstract
The immune function is closely related to iron (Fe) homeostasis and allostasis. The aim of this bioinformatics-assisted review was twofold; (i) to update the current knowledge of Fe metabolism and its relationship to the immune system, and (ii) to perform a prediction analysis of regulatory network hubs that might serve as potential biomarkers during stress-induced immunosuppression. Several literature and bioinformatics databases/repositories were utilized to review Fe metabolism and complement the molecular description of prioritized proteins. The Search Tool for the Retrieval of Interacting Genes (STRING) was used to build a protein-protein interactions network for subsequent network topology analysis. Importantly, Fe is a sensitive double-edged sword where two extremes of its nutritional status may have harmful effects on innate and adaptive immunity. We identified clearly connected important hubs that belong to two clusters: (i) presentation of peptide antigens to the immune system with the involvement of redox reactions of Fe, heme, and Fe trafficking/transport; and (ii) ubiquitination, endocytosis, and degradation processes of proteins related to Fe metabolism in immune cells (e.g., macrophages). The identified potential biomarkers were in agreement with the current experimental evidence, are included in several immunological/biomarkers databases, and/or are emerging genetic markers for different stressful conditions. Although further validation is warranted, this hybrid method (human-machine collaboration) to extract meaningful biological applications using available data in literature and bioinformatics tools should be highlighted.
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Affiliation(s)
- Diego A. Bonilla
- Research Division, Dynamical Business & Science Society—DBSS International SAS, Bogota 110311, Colombia; (Y.M.); (J.L.P.)
- Research Group in Biochemistry and Molecular Biology, Faculty of Science and Education, Universidad Distrital Francisco José de Caldas, Bogota 110311, Colombia
- Research Group in Physical Activity, Sports and Health Sciences (GICAFS), Universidad de Córdoba, Montería 230002, Colombia
- Sport Genomics Research Group, Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
| | - Yurany Moreno
- Research Division, Dynamical Business & Science Society—DBSS International SAS, Bogota 110311, Colombia; (Y.M.); (J.L.P.)
- Research Group in Biochemistry and Molecular Biology, Faculty of Science and Education, Universidad Distrital Francisco José de Caldas, Bogota 110311, Colombia
| | - Jorge L. Petro
- Research Division, Dynamical Business & Science Society—DBSS International SAS, Bogota 110311, Colombia; (Y.M.); (J.L.P.)
- Research Group in Physical Activity, Sports and Health Sciences (GICAFS), Universidad de Córdoba, Montería 230002, Colombia
| | - Diego A. Forero
- Health and Sport Sciences Research Group, School of Health and Sport Sciences, Fundación Universitaria del Área Andina, Bogotá 111221, Colombia; (D.A.F.); (C.A.O.)
| | - Salvador Vargas-Molina
- Faculty of Sport Sciences, EADE-University of Wales Trinity Saint David, 29018 Málaga, Spain;
| | - Adrián Odriozola-Martínez
- Sport Genomics Research Group, Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain;
- kDNA Genomics, Joxe Mari Korta Research Center, University of the Basque Country UPV/EHU, 20018 Donostia, Spain
| | - Carlos A. Orozco
- Health and Sport Sciences Research Group, School of Health and Sport Sciences, Fundación Universitaria del Área Andina, Bogotá 111221, Colombia; (D.A.F.); (C.A.O.)
| | - Jeffrey R. Stout
- Physiology of Work and Exercise Response (POWER) Laboratory, Institute of Exercise Physiology and Rehabilitation Science, University of Central Florida, Orlando, FL 32816, USA;
| | - Eric S. Rawson
- Department of Health, Nutrition and Exercise Science, Messiah University, Mechanicsburg, PA 17055, USA;
| | - Richard B. Kreider
- Exercise & Sport Nutrition Laboratory, Human Clinical Research Facility, Department of Health & Kinesiology, Texas A&M University, College Station, TX 77843, USA;
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22
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Liu L, Wang H, Ning J, Han J, Yu C, Guan Q. The Predictability of Cystatin C for Peripheral Arterial Disease in Chinese Population with Type 2 Diabetes Mellitus. J Diabetes Res 2022; 2022:5064264. [PMID: 35392484 PMCID: PMC8983175 DOI: 10.1155/2022/5064264] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 02/06/2022] [Accepted: 03/11/2022] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES Peripheral artery disease (PAD) in diabetic populations is a vital chronic disease all over the world due to its high morbidity and mortality. It is important to find early simple screening biomarkers and find residual risk factors that may provide a new target for prevention and treatment of PAD in diabetic patients besides traditional cardiometabolic risk factors. METHODS We performed a cross-sectional retrospective study, and a total of 1671 T2DM participants were recruited. Receiver operating characteristic analysis, stepwise logistic regression analysis, points score system, and decision curve analysis were performed to assess the risk factors for PAD. RESULTS The prevalence of PAD in the study was 7.18% (n = 120). Compared to the participants with the lowest quartile of cystatin C (CysC), the risk of developing PAD in participants with the highest quartile of CysC increased 6.339-fold. The CysC was the superior indicators to distinguish participants with PAD from those without PAD, with an AUC of 0.716. Stepwise logistic regression analysis showed that CysC was independent risk factor for PAD besides traditional risk factors. Combined exposure to these traditional risk factors and CysC was associated with a stepwise increase in the risk of developing PAD and even increased 11.976-fold in participants with the highest quintiles of combined exposure score (CES) based on traditional risk factors and CysC compared to the participants with the lowest quintiles of CES. CONCLUSIONS CysC was associated with PAD independent of potential risk factors in diabetic populations. The CysC was a reliable marker for the early screening of PAD in diabetic patients besides traditional cardiometabolic risk factors.
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Affiliation(s)
- Luna Liu
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, China
| | - Hai Wang
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Jing Ning
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, China
| | - Junming Han
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Chunxiao Yu
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Qingbo Guan
- Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, China
- Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
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Chiu LYC, Syed MH, Zamzam A, Rotstein OD, Abdin R, Laraya N, Qadura M. Perceived Challenges to Routine Uptake of the Ankle Brachial Index within Primary Care Practice. J Clin Med 2021; 10:4371. [PMID: 34640389 PMCID: PMC8509610 DOI: 10.3390/jcm10194371] [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: 07/28/2021] [Revised: 09/08/2021] [Accepted: 09/18/2021] [Indexed: 11/17/2022] Open
Abstract
(1) Introduction: The ankle-brachial index (ABI) is the most widely used method of diagnosing peripheral arterial disease (PAD). However, the uptake of ABIs has been reported to be low in primary care settings across different various healthcare settings; however, this is yet to be investigated within the Canadian context. (2) Objective: Therefore, we sought to assess the rates of ABI usage as well as perceived barriers among primary care practitioners (PCPs) in Toronto, Canada. (3) Methods: A modified questionnaire was electronically sent to 257 PCPs in the Greater Toronto Area (GTA). Questions pertained to frequency, feasibility, utility, and barriers associated with ABI usage in clinical practice. Responses were collected and tallied. (4) Results: A total of 52 PCPs completed the questionnaire. 79% of PCPs did not routinely perform ABIs within their clinical practice, and 56% deemed ABI usage as unfeasible. Constraints in time and staff personnel, as well as complexity of ABI result interpretation, were cited as the major perceived barriers to ABI usage. The overwhelming majority of PCPs viewed alternative forms of diagnosis, such as a blood test for PAD, as being preferable to ABI, as such an approach would enhance diagnostic simplicity and efficiency. (5) Conclusion: ABI usage rates are poor within primary care practices in Toronto, Canada. Alternative approaches for diagnosing PAD may result in greater adoption rates among PCPs and therefore improve the identification of patients with PAD.
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Affiliation(s)
- Lily Y. C. Chiu
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada; (L.Y.C.C.); (M.H.S.); (A.Z.)
| | - Muzammil H. Syed
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada; (L.Y.C.C.); (M.H.S.); (A.Z.)
| | - Abdelrahman Zamzam
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada; (L.Y.C.C.); (M.H.S.); (A.Z.)
| | - Ori D. Rotstein
- Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada;
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
| | - Rawand Abdin
- Department of Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada;
| | - Nadine Laraya
- Family Medicine Department, St. Joseph’s Health Centre, Toronto, ON M6R 1B5, Canada;
- Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1V7, Canada
| | - Mohammad Qadura
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada; (L.Y.C.C.); (M.H.S.); (A.Z.)
- Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada;
- Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
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Liang S, Li Q, Lai Q, Zhou Y, Zhang H, Chen X, Yao B, Xu W, Yang X. Beta-2-Microglobulin is an Independent Risk Factor for Asymptomatic Carotid Atherosclerosis in Patients with Primary Aldosteronism. J Atheroscler Thromb 2021; 29:937-952. [PMID: 34305082 PMCID: PMC9174095 DOI: 10.5551/jat.62851] [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] [Indexed: 11/11/2022] Open
Abstract
Aim: To identify the association between serum beta-2-microglobulin (B2M) or cystatin C (CysC) and asymptomatic carotid atherosclerosis in patients with primary aldosteronism (PA).
Methods: In this cross-sectional study, 265 subjects were enrolled, including 83 patients with PA, 91 with essential hypertension (EH), and 91 normotensive (NT) controls. B2M, CysC, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured, and the aldosterone-to-renin ratio (ARR) was calculated. Carotid intima-media thickness (cIMT), increased cIMT, and presence of carotid plaque or carotid stenosis ＜50% in the carotid artery were measuredvia ultrasonography to evaluate the degree of asymptomatic carotid atherosclerosis.
Results: CIMT increased in the NT, EH, and PA groups (0.60 (0.50, 0.80) mm vs. 0.80 (0.60, 1.00) mm vs. 0.90 (0.70, 1.10) mm,P＜0.01), so as the prevalence of increased cIMT and presence of carotid plaque (bothP＜0.05). The B2M and CysC levels exhibited the same trend (B2M: 1.60±0.34 mg/L, 1.80±0.41 mg/L, 1.98±0.64 mg/L,P＜0.05; CysC: 0.76±0.12 mg/L, 0.88±0.17 mg/L, 0.94±0.23 mg/L,P＜0.05). B2M, CysC, PAC, and ARR were all positively associated with cIMT (allP＜0.01) in the PA group. After adjusting for potential confounders, B2M, PAC, but not CysC or ARR were independently associated with increased cIMT and presence of carotid plaque and carotid stenosis ＜50%, respectively. The receiver operating characteristic (ROC) curve analysis revealed that B2M and PAC demonstrated significant predictive ability for increased cIMT and presence of carotid plaque and carotid stenosis ＜50%.
Conclusion: B2M is an independent risk factor for asymptomatic carotid atherosclerosis in patients with PA.
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Affiliation(s)
- Shangyan Liang
- Department of VIP Medical Service Center, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Qingling Li
- Department of VIP Medical Service Center, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Qianwei Lai
- Department of VIP Medical Service Center, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Ying Zhou
- Department of VIP Medical Service Center, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Hui Zhang
- Department of Ultrasound, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Xueyan Chen
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Bin Yao
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Wen Xu
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University
| | - Xubin Yang
- Department of Endocrinology and Metabolism, the 3rd Affiliated Hospital of Sun Yat-sen University
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25
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An integrated quantitative proteomics strategy reveals the dual mechanisms of celastrol against acute inflammation. CHINESE CHEM LETT 2021. [DOI: 10.1016/j.cclet.2020.11.064] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
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Abstract
Atherosclerotic lower extremity peripheral artery disease (PAD) is increasingly recognized as an important cause of cardiovascular morbidity and mortality that affects >230 million people worldwide. Traditional cardiovascular risk factors, including advanced age, smoking, and diabetes, are strongly linked to an increase risk of PAD. Although PAD has been historically underappreciated compared with coronary artery disease and stroke, greater attention on PAD in recent years has led to important new epidemiological insights in the areas of thrombosis, inflammation, dyslipidemia, and microvascular disease. In addition, the concept of polyvascular disease, or clinically evident atherosclerosis in multiple arterial beds, is increasingly identified as a particularly malignant cardiovascular disease worthy of special clinical attention and further study. It is noteworthy that PAD may increase the risk of adverse outcomes in similar or even greater magnitude than coronary disease or stroke. In this review, we highlight important new advances in the epidemiology of PAD with a particular focus on polyvascular disease, emerging biomarkers, and differential risk pathways for PAD compared with other atherosclerotic diseases.
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Affiliation(s)
- Aaron W Aday
- Division of Cardiovascular Medicine, Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University Medical Center, Nashville, TN (A.W.A.)
| | - Kunihiro Matsushita
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (K.M.)
- Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD (K.M.)
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27
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Renal Replacement Modality Affects Uremic Toxins and Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021. [DOI: 10.1155/2021/6622179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Nowadays, the high prevalence of kidney diseases and their related complications, including endothelial dysfunction and cardiovascular disease, represents one of the leading causes of death in patients with chronic kidney diseases. Renal failure leads to accumulation of uremic toxins, which are the main cause of oxidative stress development. The renal replacement therapy appears to be the best way to lower uremic toxin levels in patients with end-stage renal disease and reduce oxidative stress. At this moment, despite the increasing number of recognized toxins and their mechanisms of action, it is impossible to determine which of them are the most important and which cause the greatest complications. There are many different types of renal replacement therapy, but the best treatment has not been identified yet. Patients treated with diffusion methods have satisfactory clearance of small molecules, but the clearance of medium molecules appears to be insufficient, but treatment with convection methods cleans medium molecules better than small molecules. Hence, there is an urgent need of new more validated, appropriate, and reliable information not only on toxins and their role in metabolic disorders, including oxidative stress, but also on the best artificial renal replacement therapy to reduce complications and prolong the life of patients with chronic kidney disease.
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Brioschi M, Gianazza E, Agostoni P, Zoanni B, Mallia A, Banfi C. Multiplexed MRM-Based Proteomics Identified Multiple Biomarkers of Disease Severity in Human Heart Failure. Int J Mol Sci 2021; 22:ijms22020838. [PMID: 33467687 PMCID: PMC7830442 DOI: 10.3390/ijms22020838] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 01/12/2021] [Indexed: 01/09/2023] Open
Abstract
Heart failure (HF) is a complex disease due to the intricate interplay of several mechanisms, which therefore implies the need for a multimarker strategy to better personalize the care of patients with HF. In this study, we developed a targeted mass spectrometry approach based on multiple reaction monitoring (MRM) to measure multiple circulating protein biomarkers, involved in cardiovascular disease, to address their relevance in the human HF, intending to assess the feasibility of the workflow in the disease monitoring and risk stratification. In this study, we analyzed a total of 60 plasma proteins in 30 plasma samples from eight control subjects and 22 age- and gender- matched HF patients. We identified a panel of four plasma proteins, namely Neuropilin-2, Beta 2 microglobulin, alpha-1-antichymotrypsin, and complement component C9, that were more abundant in HF patients in relation to disease severity and pulmonary dysfunction. Moreover, we showed the ability of the combination of these candidate proteins to discriminate, with sufficient accuracy, HF patients from healthy subjects. In conclusion, we demonstrated the feasibility and potential of a proteomic workflow based on MRM mass spectrometry for the evaluation of multiple proteins in human plasma and the identification of a panel of biomarkers of HF severity.
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Affiliation(s)
- Maura Brioschi
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (M.B.); (E.G.); (P.A.); (B.Z.); (A.M.)
| | - Erica Gianazza
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (M.B.); (E.G.); (P.A.); (B.Z.); (A.M.)
| | - Piergiuseppe Agostoni
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (M.B.); (E.G.); (P.A.); (B.Z.); (A.M.)
- Dipartimento di Scienze Cliniche e di Comunità, Sezione Cardiovascolare, Università di Milano, 20122 Milano, Italy
| | - Beatrice Zoanni
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (M.B.); (E.G.); (P.A.); (B.Z.); (A.M.)
| | - Alice Mallia
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (M.B.); (E.G.); (P.A.); (B.Z.); (A.M.)
| | - Cristina Banfi
- Centro Cardiologico Monzino, IRCCS, 20138 Milano, Italy; (M.B.); (E.G.); (P.A.); (B.Z.); (A.M.)
- Correspondence: ; Tel.: +39-0258002403; Fax: +39-0258002623
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Targeting Uremic Toxins to Prevent Peripheral Vascular Complications in Chronic Kidney Disease. Toxins (Basel) 2020; 12:toxins12120808. [PMID: 33419312 PMCID: PMC7765928 DOI: 10.3390/toxins12120808] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 12/14/2020] [Accepted: 12/16/2020] [Indexed: 12/24/2022] Open
Abstract
Chronic kidney disease (CKD) exhibits progressive kidney dysfunction and leads to disturbed homeostasis, including accumulation of uremic toxins, activated renin-angiotensin system, and increased oxidative stress and proinflammatory cytokines. Patients with CKD are prone to developing the peripheral vascular disease (PVD), leading to poorer outcomes than those without CKD. Cumulative evidence has showed that the synergy of uremic milieu and PVD could exaggerate vascular complications such as limb ischemia, amputation, stenosis, or thrombosis of a dialysis vascular access, and increase mortality risk. The role of uremic toxins in the pathogenesis of vascular dysfunction in CKD has been investigated. Moreover, growing evidence has shown the promising role of uremic toxins as a therapeutic target for PVD in CKD. This review focused on uremic toxins in the pathophysiology, in vitro and animal models, and current novel clinical approaches in reducing the uremic toxin to prevent peripheral vascular complications in CKD patients.
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30
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Ghantous CM, Kamareddine L, Farhat R, Zouein FA, Mondello S, Kobeissy F, Zeidan A. Advances in Cardiovascular Biomarker Discovery. Biomedicines 2020; 8:biomedicines8120552. [PMID: 33265898 PMCID: PMC7759775 DOI: 10.3390/biomedicines8120552] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/18/2020] [Accepted: 11/20/2020] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular diseases are the leading causes of mortality worldwide. Among them, hypertension and its pathological complications pose a major risk for the development of other cardiovascular diseases, including heart failure and stroke. Identifying novel and early stage biomarkers of hypertension and other cardiovascular diseases is of paramount importance in predicting and preventing the major morbidity and mortality associated with these diseases. Biomarkers of such diseases or predisposition to their development are identified by changes in a specific indicator’s expression between healthy individuals and patients. These include changes in protein and microRNA (miRNA) levels. Protein profiling using mass spectrometry and miRNA screening utilizing microarray and sequencing have facilitated the discovery of proteins and miRNA as biomarker candidates. In this review, we summarized some of the different, promising early stage protein and miRNA biomarker candidates as well as the currently used biomarkers for hypertension and other cardiovascular diseases. Although a number of promising markers have been identified, it is unlikely that a single biomarker will unambiguously aid in the classification of these diseases. A multi-marker panel-strategy appears useful and promising for classifying and refining risk stratification among patients with cardiovascular disease.
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Affiliation(s)
- Crystal M. Ghantous
- Department of Nursing and Health Sciences, Faculty of Nursing and Health Sciences, Notre Dame University-Louaize, Keserwan 72, Lebanon;
| | - Layla Kamareddine
- Biomedical Sciences Department, College of Health Sciences, QU Health, Qatar University, Doha 2713, Qatar;
- Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha 2713, Qatar
| | - Rima Farhat
- Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon;
| | - Fouad A. Zouein
- Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon;
| | - Stefania Mondello
- Oasi Research Institute-IRCCS, 94018 Troina, Italy;
- Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, 98125 Messina, Italy
| | - Firas Kobeissy
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon;
| | - Asad Zeidan
- Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha 2713, Qatar
- Department of Basic Medical Science, Faculty of Medicine, QU Health, Qatar University, Doha 2713, Qatar
- Correspondence: ; Tel.: +97-431-309-19
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Ceasovschih A, Sorodoc V, Onofrei (Aursulesei) V, Tesloianu D, Tuchilus C, Anisie E, Petris A, Statescu C, Jaba E, Stoica A, Grigorescu ED, Jaba IM, Sorodoc L. Biomarker Utility for Peripheral Artery Disease Diagnosis in Real Clinical Practice: A Prospective Study. Diagnostics (Basel) 2020; 10:E723. [PMID: 32962217 PMCID: PMC7555404 DOI: 10.3390/diagnostics10090723] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/16/2020] [Accepted: 09/19/2020] [Indexed: 12/24/2022] Open
Abstract
Peripheral arterial disease (PAD) is a common manifestation of generalized atherosclerosis, which affects more than 200 million patients worldwide. Currently, there is no ideal biomarker for PAD risk stratification and diagnosis. The goal of this research was to investigate the levels of inflammation biomarkers and cystatin C and to explore their utility for the diagnosis of PAD. The study included 296 participants, distributed in two groups: 216 patients diagnosed with PAD and 80 patients without PAD as controls. All studied biomarker levels (C-reactive protein, CRP; fibrinogen; erythrocyte sedimentation rate, ESR; neopterin; beta 2-microglobulin, B2-MG; and cystatin C) were significantly higher in the PAD group and indirectly correlated with the ankle-brachial index (ABI). The final logistic regression model included an association of neopterin, fibrinogen, and cystatin C as the most efficient markers for the prediction of PAD diagnosis. When comparing the area under the curve (AUC) for all biomarkers, the value for neopterin was significantly higher than those of all the other analyzed biomarkers. In agreement with previous studies, this research shows that markers such as fibrinogen, CRP, ESR, B2-MG, and cystatin C have significant value for the diagnosis of PAD, and also clearly underlines the accuracy of neopterin as a leading biomarker in PAD prediction.
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Affiliation(s)
- Alexandr Ceasovschih
- Department of Internal Medicine, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania; (A.C.); (A.S.); (L.S.)
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
| | - Victorita Sorodoc
- Department of Internal Medicine, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania; (A.C.); (A.S.); (L.S.)
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
| | - Viviana Onofrei (Aursulesei)
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
- Department of Cardiology, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania;
| | - Dan Tesloianu
- Department of Cardiology, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania;
| | - Cristina Tuchilus
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
- Department of Microbiology/Immunology, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania;
| | - Ecaterina Anisie
- Department of Microbiology/Immunology, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania;
| | - Antoniu Petris
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
- Department of Cardiology, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania;
| | - Cristian Statescu
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
- Department of Cardiology, Cardiovascular Diseases Institute “Prof. Dr. George I.M. Georgescu”, 700503 Iași, Romania
| | - Elisabeta Jaba
- Department of Statistics, Alexandru Ioan Cuza University, 700506 Iasi, Romania;
| | - Alexandra Stoica
- Department of Internal Medicine, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania; (A.C.); (A.S.); (L.S.)
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
| | - Elena-Daniela Grigorescu
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
- Department of Diabetology, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania
| | | | - Laurentiu Sorodoc
- Department of Internal Medicine, Clinical Emergency Hospital “Sfantul Spiridon”, 700106 Iasi, Romania; (A.C.); (A.S.); (L.S.)
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania; (V.O.); (C.T.); (A.P.); (C.S.); (E.-D.G.)
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Rueda F, Borràs E, García-García C, Iborra-Egea O, Revuelta-López E, Harjola VP, Cediel G, Lassus J, Tarvasmäki T, Mebazaa A, Sabidó E, Bayés-Genís A. Protein-based cardiogenic shock patient classifier. Eur Heart J 2019; 40:2684-2694. [DOI: 10.1093/eurheartj/ehz294] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 01/04/2019] [Accepted: 04/19/2019] [Indexed: 11/15/2022] Open
Abstract
Abstract
Aims
Cardiogenic shock (CS) is associated with high short-term mortality and a precise CS risk stratification could guide interventions to improve patient outcome. Here, we developed a circulating protein-based score to predict short-term mortality risk among patients with CS.
Methods and results
Mass spectrometry analysis of 2654 proteins was used for screening in the Barcelona discovery cohort (n = 48). Targeted quantitative proteomics analyses (n = 51 proteins) were used in the independent CardShock cohort (n = 97) to derive and cross-validate the protein classifier. The combination of four circulating proteins (Cardiogenic Shock 4 proteins—CS4P), discriminated patients with low and high 90-day risk of mortality. CS4P comprises the abundances of liver-type fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1. Within the CardShock cohort used for internal validation, the C-statistic was 0.78 for the CardShock risk score, 0.83 for the CS4P model, and 0.84 (P = 0.033 vs. CardShock risk score) for the combination of CardShock risk score with the CS4P model. The CardShock risk score with the CS4P model showed a marked benefit in patient reclassification, with a net reclassification improvement (NRI) of 0.49 (P = 0.020) compared with CardShock risk score. Similar reclassification metrics were observed in the IABP-SHOCK II risk score combined with CS4P (NRI =0.57; P = 0.032). The CS4P patient classification power was confirmed by enzyme-linked immunosorbent assay (ELISA).
Conclusion
A new protein-based CS patient classifier, the CS4P, was developed for short-term mortality risk stratification. CS4P improved predictive metrics in combination with contemporary risk scores, which may guide clinicians in selecting patients for advanced therapies.
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Affiliation(s)
- Ferran Rueda
- Heart Institute, Hospital Universitari Germans Trias i Pujol, c/ Canyet SN, 08916 Badalona, Spain
- Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
| | - Eva Borràs
- Proteomics Unit, Centre de Regulació Genòmica (CRG), Barcelona Institute of Science and Technology (BIST), Dr Aiguader 88, Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Dr Aiguader 88, Barcelona, Spain
| | - Cosme García-García
- Heart Institute, Hospital Universitari Germans Trias i Pujol, c/ Canyet SN, 08916 Badalona, Spain
- Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
| | - Oriol Iborra-Egea
- Heart Institute, Hospital Universitari Germans Trias i Pujol, c/ Canyet SN, 08916 Badalona, Spain
- Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
| | - Elena Revuelta-López
- Heart Institute, Hospital Universitari Germans Trias i Pujol, c/ Canyet SN, 08916 Badalona, Spain
- Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
| | - Veli-Pekka Harjola
- Emergency Medicine, Department of Emergency Medicine and Services, University of Helsinki, Helsinki University Hospital, Finland
| | - Germán Cediel
- Heart Institute, Hospital Universitari Germans Trias i Pujol, c/ Canyet SN, 08916 Badalona, Spain
- Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
| | - Johan Lassus
- Cardiology, University of Helsinki, Heart and Lung Center, Helsinki University Hospital, Finland
| | - Tuukka Tarvasmäki
- Cardiology, University of Helsinki, Heart and Lung Center, Helsinki University Hospital, Finland
| | - Alexandre Mebazaa
- U942 Inserm, University Paris Diderot, APHP Hôpitaux Universitaires Saint-Louis-Lariboisière, INI-CRCT, Paris, France
| | - Eduard Sabidó
- Proteomics Unit, Centre de Regulació Genòmica (CRG), Barcelona Institute of Science and Technology (BIST), Dr Aiguader 88, Barcelona, Spain
- Universitat Pompeu Fabra (UPF), Dr Aiguader 88, Barcelona, Spain
| | - Antoni Bayés-Genís
- Heart Institute, Hospital Universitari Germans Trias i Pujol, c/ Canyet SN, 08916 Badalona, Spain
- Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain
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Qun S, Hu F, Wang G, Wu J, Tang Q, Zhang J, Chen Z, Wang X, Liu Q, Ge W. Serum beta2-microglobulin levels are highly associated with the risk of acute ischemic stroke. Sci Rep 2019; 9:6883. [PMID: 31053801 PMCID: PMC6499788 DOI: 10.1038/s41598-019-43370-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 04/23/2019] [Indexed: 12/19/2022] Open
Abstract
Inflammation is considered an important mechanism of cell death or survival after ischemic stroke. As an important marker of inflammation, the role of β2-microglobulin (β2M) in acute ischemic stroke is unclear. We investigated the relationship between serum β2M and the risk of acute ischemic stroke (AIS). Patients with AIS (202 cases), intracerebral hemorrhage (ICH, 41 cases), and healthy controls (253 cases) were recruited. Clinical and biochemical characteristics were collected. We used three binary logistic regression models to evaluate the correlation of β2M with the risk of AIS. Furthermore, we investigated the relationship between serum β2M and the National Institute of Health Stroke Scale (NIHSS) score, the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) subtypes, and the Essen Stroke Risk Score (ESRS) in patients with AIS. Our results showed that serum β2M levels in patients with AIS were much higher than those in patients with ICH and in the control subjects. Individuals with higher levels of β2M had higher odds of AIS. Moreover, serum β2M levels were significantly and positively correlated with ESRS. In addition, the levels of β2M were varied with different subgroups of AIS (TOAST classification). Serum β2M is highly associated with the risk of AIS.
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Affiliation(s)
- Sen Qun
- Department of Neurology, The First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), Hefei City, Anhui, China. .,Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University, Hefei City, Anhui, China.
| | - Fuyong Hu
- School of Public Health, Bengbu Medical College, Bengbu City, Anhui, China
| | - Guoping Wang
- Department of Neurology, The First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), Hefei City, Anhui, China
| | - Juncang Wu
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University, Hefei City, Anhui, China
| | - Qiqiang Tang
- Department of Neurology, The First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), Hefei City, Anhui, China
| | - Ji Zhang
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University, Hefei City, Anhui, China
| | - Zhengxu Chen
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University, Hefei City, Anhui, China
| | - Xiaoqiang Wang
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University, Hefei City, Anhui, China
| | - Qiuwan Liu
- Department of Neurology, The Hefei Affiliated Hospital of Anhui Medical University, Hefei City, Anhui, China
| | - Wei Ge
- Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, China.
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Beta 2-Microglobulin and the Severity of Coronary Stenosis in Patients With Acute Coronary Syndrome. Heart Lung Circ 2019; 28:575-582. [DOI: 10.1016/j.hlc.2018.02.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 02/20/2018] [Indexed: 11/23/2022]
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Toxines urémiques de moyen poids moléculaire : un véritable regain d’intérêt. Nephrol Ther 2019; 15:82-90. [DOI: 10.1016/j.nephro.2018.09.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 09/02/2018] [Indexed: 01/20/2023]
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Hilt ZT, Pariser DN, Ture SK, Mohan A, Quijada P, Asante AA, Cameron SJ, Sterling JA, Merkel AR, Johanson AL, Jenkins JL, Small EM, McGrath KE, Palis J, Elliott MR, Morrell CN. Platelet-derived β2M regulates monocyte inflammatory responses. JCI Insight 2019; 4:122943. [PMID: 30702442 PMCID: PMC6483513 DOI: 10.1172/jci.insight.122943] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 01/25/2019] [Indexed: 12/13/2022] Open
Abstract
β-2 Microglobulin (β2M) is a molecular chaperone for the major histocompatibility class I (MHC I) complex, hemochromatosis factor protein (HFE), and the neonatal Fc receptor (FcRn), but β2M may also have less understood chaperone-independent functions. Elevated plasma β2M has a direct role in neurocognitive decline and is a risk factor for adverse cardiovascular events. β2M mRNA is present in platelets at very high levels, and β2M is part of the activated platelet releasate. In addition to their more well-studied thrombotic functions, platelets are important immune regulatory cells that release inflammatory molecules and contribute to leukocyte trafficking, activation, and differentiation. We have now found that platelet-derived β2M is a mediator of monocyte proinflammatory differentiation through noncanonical TGFβ receptor signaling. Circulating monocytes from mice lacking β2M only in platelets (Plt-β2M-/-) had a more proreparative monocyte phenotype, in part dependent on increased platelet-derived TGFβ signaling in the absence of β2M. Using a mouse myocardial infarction (MI) model, Plt-β2M-/- mice had limited post-MI proinflammatory monocyte responses and, instead, demonstrated early proreparative monocyte differentiation, profibrotic myofibroblast responses, and a rapid decline in heart function compared with WT mice. These data demonstrate a potentially novel chaperone-independent, monocyte phenotype-regulatory function for platelet β2M and that platelet-derived 2M and TGFβ have opposing roles in monocyte differentiation that may be important in tissue injury responses.
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Affiliation(s)
| | | | | | - Amy Mohan
- Aab Cardiovascular Research Institute
| | | | - Akua A. Asante
- Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York, USA
| | | | - Julie A. Sterling
- Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA
- Department of Cancer Biology, Medicine, Division of Clinical Pharmacology, Bone Biology Center, and Biomedical Engineering, and
- Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA
| | - Alyssa R. Merkel
- Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA
- Department of Cancer Biology, Medicine, Division of Clinical Pharmacology, Bone Biology Center, and Biomedical Engineering, and
- Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA
| | | | | | | | - Kathleen E. McGrath
- Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York, USA
| | - James Palis
- Center for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester School of Medicine, Rochester, New York, USA
| | - Michael R. Elliott
- Department of Microbiology and Immunology, University of Rochester School of Medicine, Rochester, New York, USA
| | - Craig N. Morrell
- Aab Cardiovascular Research Institute
- Department of Microbiology and Immunology, University of Rochester School of Medicine, Rochester, New York, USA
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Two years of maintenance hemodialysis has a pronounced effect on arterial stiffness progression. Aging Clin Exp Res 2019; 31:193-199. [PMID: 29779091 DOI: 10.1007/s40520-018-0971-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 05/09/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND The change of aortic stiffness, but not the particular baseline value, plays a crucial role in estimating the patient risk with end-stage renal disease. Therefore, we aimed to analyze the evolution of central and peripheral arterial stiffness in hemodialysis population without previous cardiovascular events during a 2-year follow-up. METHODS 60 hemodialysis patients (mean age 57.61 ± 13.01 years) were prospectively interviewed, and they underwent blood tests, chest X-ray for aortic calcification evaluation and pulse wave velocity (PWV) measurements at the baseline, after 6 months and after 2 years of observation period. RESULTS We found significant progression of aortic PWV (12.73 vs. 14.24 m/s, p = 0.032) and regression of brachial PWV (11.53 vs. 8.85 m/s, p < 0.001). CRP increase influenced evolution of aortic PWV (β = 0.331, p = 0.031, R2 = 0.599). Higher β2-microglobulin values was related to the progression of aortic PWV (β = 0.219, p = 0.022, R2 = 0.568). Mean arterial blood pressure had influence only on the short-term arterial stiffness evolution. CONCLUSIONS Patients on maintenance hemodialysis experience pronounced changes of arterial stiffness during the 2-year follow-up period. The progression of aortic stiffness is related to inflammatory response and particularly is influenced by β2-microglobulin concentration and aortic calcification.
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Ali H, Kishore B, Baharani J. Significance of paraprotein gap and β2 microglobulins in predialysis Population with multiple myeloma. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2019; 30:825-831. [DOI: 10.4103/1319-2442.265458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Leffers HCB, Hermansen ML, Sandholt B, Fuchs A, Sillesen H, Køber L, Kofoed KF, Faurschou M, Jacobsen S. Plasma levels of β2-microglobulin are associated with atherosclerosis in patients with systemic lupus erythematosus: a cross-sectional cohort study. Lupus 2018; 27:1517-1523. [PMID: 29954284 DOI: 10.1177/0961203318784661] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective The objective of this paper is to examine the association between plasma levels of β2-microglobulin (β2MG), a protein previously associated with atherosclerosis, and the presence of carotid plaque (CP) or coronary artery calcium (CAC) in a cross-sectional cohort study of patients with systemic lupus erythematosus (SLE). Methods Patients with SLE were enrolled between June 2013 and May 2014. The presence of CP and CAC was assessed with ultrasonography and computed tomography scan, respectively. The presence of CP or CAC in the SLE patients was analyzed with respect to plasma levels of β2MG and renal function expressed as the estimated glomerular filtration rate (eGFR). Results The study cohort consisted of 147 patients, 89% women and 95% Caucasians. The median age was 46 (range: 21-75) years with a median disease duration of 14 years. CP and CAC was observed in 29 (20%) and 57 (39%) of patients, respectively. CP or CAC was seen in 62 (42%) patients and was associated with the highest quartile of plasma β2MG in patients with eGFR ≥ 90 ml/min/1.73 m2; OR = 18 (95% CI: 1.7-181). β2MG adjusted for eGFR was also associated with presence of CP or CAC in the total cohort. The exclusion of 25 patients with a prior history of cardiovascular disease did not change the observed associations. Conclusion In this study, we found significant associations between imaging markers of atherosclerosis and high plasma levels of plasma β2MG. These data suggest that β2MG is a candidate for further study as a biomarker for atherosclerosis in SLE.
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Affiliation(s)
- H C B Leffers
- 1 Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - M L Hermansen
- 1 Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - B Sandholt
- 2 Department of Vascular Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - A Fuchs
- 3 Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - H Sillesen
- 2 Department of Vascular Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - L Køber
- 3 Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - K F Kofoed
- 3 Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.,4 Department of Radiology, The Diagnostic Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - M Faurschou
- 1 Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - S Jacobsen
- 1 Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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Li G, Morris-Blanco KC, Lopez MS, Yang T, Zhao H, Vemuganti R, Luo Y. Impact of microRNAs on ischemic stroke: From pre- to post-disease. Prog Neurobiol 2018; 163-164:59-78. [PMID: 28842356 PMCID: PMC11884751 DOI: 10.1016/j.pneurobio.2017.08.002] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 06/12/2017] [Accepted: 08/16/2017] [Indexed: 12/21/2022]
Abstract
Stroke is the number one cause of neurological dysfunction in adults and has a heavy socioeconomic burden worldwide. The etiological origins of ischemic stroke and resulting pathological processes are mediated by a multifaceted cascade of molecular mechanisms that are in part modulated by posttranscriptional activity. Accumulating evidence has revealed a role for microRNAs (miRNAs) as essential mediators of posttranscriptional gene silencing in both the physiology of brain development and pathology of ischemic stroke. In this review, we compile miRNAs that have been reported to regulate various stroke risk factors and pre-disease mechanisms, including hypertension, atherosclerosis, and diabetes, followed by an in-depth analysis of miRNAs in ischemic stroke pathogenesis, such as excitotoxicity, oxidative stress, inflammation, apoptosis, angiogenesis and neurogenesis. Since promoting or suppressing expression of miRNAs by specific pharmaceutical and non-pharmaceutical therapies may be beneficial to post-stroke recovery, we also highlight the potential therapeutic value of miRNAs in clinical settings.
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Affiliation(s)
- Guangwen Li
- Cerebrovascular Diseases Research Institute and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 10053, China
| | | | - Mary S Lopez
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA; Cellular and Molecular Pathology Graduate Program, University of Wisconsin, Madison, WI, USA
| | - Tuo Yang
- Department of Neurology, University of Pittsburgh School of Medicine, PA, USA
| | - Haiping Zhao
- Cerebrovascular Diseases Research Institute and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 10053, China
| | - Raghu Vemuganti
- Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA; Cellular and Molecular Pathology Graduate Program, University of Wisconsin, Madison, WI, USA; William S. Middleton VA Hospital, Madison, WI, USA.
| | - Yumin Luo
- Cerebrovascular Diseases Research Institute and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 10053, China; Beijing Institute for Brain Disorders and Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing 10053, China.
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Raikou VD, Kyriaki D. Mortality and Low Serum Bicarbonate Level in Patients on Hemodiafiltration versus Peritoneal Dialysis. Indian J Nephrol 2018; 28:105-112. [PMID: 29861560 PMCID: PMC5952448 DOI: 10.4103/ijn.ijn_232_16] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Mortality is substantially elevated in patients on chronic kidney disease in comparison to general population. In this study, we observed the mortality rate in relation to risk factors including low serum bicarbonate level, coronary artery disease (CAD), and dialysis modality in patients on dialysis during a median follow-up time of 60 months. We studied 96 dialysis patients, 62 males and 34 females, on mean age 62.1 ± 14.27 years old. The treatment modalities which were applied were predilution hemodiafiltration (HDF, n = 76), and peritoneal dialysis (PD, n = 20). We performed Kaplan-Meier curves and a Cox-regression analysis to investigate significant risk factors for mortality including hypertension, diabetes mellitus, smoking, bone disease defined by intact-parathormone, serum albumin, serum bicarbonate levels < or >22 mEq/L, dialysis modality, and the existence of CAD. Cox-regression analysis revealed a significant impact of serum bicarbonate levels <22 mEq/L on mortality in combination to dialysis modality and CAD. The prevalence of CAD on mortality was found significant (log-rank = 5.507, P = 0.02). Furthermore, the impact of dialysis modality on mortality was shown significant (log rank = 22.4, P = 0.001), noting that during the first 28-30 months from the treatment initiation, the survival was better for PD; but then, the mortality was significantly increased comparatively to HDF. Uncorrected metabolic acidosis and CAD were shown as independent significant predictors for mortality in patients on renal replacement therapy. PD may provide worse survival after 2-2.5 years of treatment initiation than HDF.
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Affiliation(s)
- V D Raikou
- 1st Department of Medicine-Propaedaetic, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, Greece
| | - D Kyriaki
- Department of Nuclear Medicine, General Hospital "LAΪKO", Athens, Greece
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Liu Y, Liao J, Ku T, Li X, Sheppard AM. Assessment of milk quality using novel mutations of B2M gene in bovine DNA from milk. CYTA - JOURNAL OF FOOD 2018. [DOI: 10.1080/19476337.2017.1394367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Yongfeng Liu
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, PR China
| | - Jing Liao
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, PR China
| | - Ting Ku
- College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an, PR China
| | - Xiaoling Li
- Liggins Institute, University of Auckland, Auckland, New Zealand
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Vanholder R, Pletinck A, Schepers E, Glorieux G. Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update. Toxins (Basel) 2018; 10:33. [PMID: 29316724 PMCID: PMC5793120 DOI: 10.3390/toxins10010033] [Citation(s) in RCA: 222] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 12/21/2017] [Accepted: 12/23/2017] [Indexed: 02/07/2023] Open
Abstract
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [β₂-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.
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Affiliation(s)
- Raymond Vanholder
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
| | - Anneleen Pletinck
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
| | - Eva Schepers
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
| | - Griet Glorieux
- Nephrology Section, Department of Internal Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
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45
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Yang C, Kwak L, Ballew SH, Garimella PS, Jaar BG, Folsom AR, Heiss G, Selvin E, Lutsey PL, Coresh J, Matsushita K. Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease. Atherosclerosis 2017; 267:167-174. [PMID: 28992939 PMCID: PMC5705382 DOI: 10.1016/j.atherosclerosis.2017.09.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 08/25/2017] [Accepted: 09/19/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. METHODS Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.
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Affiliation(s)
- Chao Yang
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Lucia Kwak
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | | | | | | | - Aaron R Folsom
- University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Gerardo Heiss
- University of North Carolina at Chapel Hill Gillings School of Global Public Health, Chapel Hill, NC, USA
| | - Elizabeth Selvin
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Pamela L Lutsey
- University of Minnesota School of Public Health, Minneapolis, MN, USA
| | - Josef Coresh
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Johns Hopkins School of Medicine, Baltimore, MD, USA
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46
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Huang G, Willems K, Soskine M, Wloka C, Maglia G. Electro-osmotic capture and ionic discrimination of peptide and protein biomarkers with FraC nanopores. Nat Commun 2017; 8:935. [PMID: 29038539 PMCID: PMC5715100 DOI: 10.1038/s41467-017-01006-4] [Citation(s) in RCA: 195] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 08/09/2017] [Indexed: 12/13/2022] Open
Abstract
Biological nanopores are nanoscale sensors employed for high-throughput, low-cost, and long read-length DNA sequencing applications. The analysis and sequencing of proteins, however, is complicated by their folded structure and non-uniform charge. Here we show that an electro-osmotic flow through Fragaceatoxin C (FraC) nanopores can be engineered to allow the entry of polypeptides at a fixed potential regardless of the charge composition of the polypeptide. We further use the nanopore currents to discriminate peptide and protein biomarkers from 25 kDa down to 1.2 kDa including polypeptides differing by one amino acid. On the road to nanopore proteomics, our findings represent a rationale for amino-acid analysis of folded and unfolded polypeptides with nanopores. Biological nanopore–based protein sequencing and recognition is challenging due to the folded structure or non-uniform charge of peptides. Here the authors show that engineered FraC nanopores can overcome these problems and recognize biomarkers in the form of oligopeptides, polypeptides and folded proteins.
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Affiliation(s)
- Gang Huang
- Groningen Biomolecular Sciences & Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands
| | - Kherim Willems
- KU Leuven Department of Chemistry, Celestijnenlaan 200G, 3001, Leuven, Belgium.,Imec, Kapeldreef 75, 3001, Leuven, Belgium
| | - Misha Soskine
- Groningen Biomolecular Sciences & Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands
| | - Carsten Wloka
- Groningen Biomolecular Sciences & Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands.
| | - Giovanni Maglia
- Groningen Biomolecular Sciences & Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands.
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47
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Li JY, Yang XY, Wang XF, Jia X, Wang ZJ, Deng AP, Bai XL, Zhu L, Li BH, Feng ZB, Li Y, Wang L, Jin S. Siglec-5 is a novel marker of critical limb ischemia in patients with diabetes. Sci Rep 2017; 7:11272. [PMID: 28900239 PMCID: PMC5595823 DOI: 10.1038/s41598-017-11820-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 08/30/2017] [Indexed: 11/09/2022] Open
Abstract
Critical Limb Ischemia (CLI) is common but uncommonly diagnosed. Improved recognition and early diagnostic markers for CLI are needed. Therefore, the aim of our study was to identify plasma biomarkers of CLI in patients with type 2 diabetes mellitus (T2DM). In this study, antibody-coated glass slide arrays were used to determine the plasma levels of 274 human cytokines in four matched cases of diabetes with and without CLI. Potential biomarkers were confirmed in an independent cohort by ELISA. After adjusting for confounding risk factors, only plasma level of Siglec-5 remained significantly associated with an increased odds ratio (OR) for diabetes with CLI by binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off points for Siglec-5 was 153.1 ng/ml. After entering Siglec-5, the AUC was 0.99, which was higher than that of confounding risk factors only (AUC = 0.97, P < 0.05). Siglec-5 was expressed in plaques, but not in healthy artery wall in T2DM patients. Elevated plasma Siglec-5 was independently associated with CLI in T2DM. Plasma Siglec-5 levels are implicated as an early diagnostic marker of CLI in T2DM patients and it may become a target for the prevention or treatment of CLI in diabetes.
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Affiliation(s)
- Ju-Yi Li
- Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Department of Pharmacy, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiao-Yan Yang
- Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiu-Fang Wang
- Department of Pain, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiong Jia
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhong-Jing Wang
- Department of Endocrinology, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ai-Ping Deng
- Department of Pharmacy, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiang-Li Bai
- Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lin Zhu
- Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Bing-Hui Li
- Department of Wound Repair, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zi-Bo Feng
- Department of Wound Repair, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ye Li
- Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ling Wang
- Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Si Jin
- Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. .,Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Gibson DS, Drain S, Kelly C, McGilligan V, McClean P, Atkinson SD, Murray E, McDowell A, Conway C, Watterson S, Bjourson AJ. Coincidence versus consequence: opportunities in multi-morbidity research and inflammation as a pervasive feature. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2017. [DOI: 10.1080/23808993.2017.1338920] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- David S. Gibson
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Stephen Drain
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Catriona Kelly
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Victoria McGilligan
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Paula McClean
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Sarah D. Atkinson
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Elaine Murray
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Andrew McDowell
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Caroline Conway
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Steven Watterson
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
| | - Anthony J. Bjourson
- Northern Ireland Centre for Stratified Medicine, Altnagelvin Hospital Campus, Ulster University, Londonderry, UK
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Rist PM, Jiménez MC, Rexrode KM. Prospective association between β 2-microglobulin levels and ischemic stroke risk among women. Neurology 2017; 88:2176-2182. [PMID: 28490653 DOI: 10.1212/wnl.0000000000004006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 03/16/2017] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVE To determine whether elevated β2-microglobulin (B2M) levels were associated with an increased risk of incident ischemic stroke events among women. METHODS We performed a nested case-control study among women enrolled in the Nurses' Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. We measured B2M levels in 473 ischemic strokes cases confirmed by medical record review and in 473 controls matched 1:1 to the cases on age, race, date of blood collection, menopausal status, postmenopausal hormone use, and smoking status. We analyzed the association between B2M and ischemic stroke using multivariable conditional logistic regression to adjust for traditional stroke risk factors. RESULTS Median levels of B2M were higher among cases (1.86 mg/L) than controls (1.80 mg/L, p = 0.009, Wilcoxon rank-sum test). Women in the highest B2M quartile had a multivariable-adjusted increased risk of ischemic stroke compared to those in the lowest quartile (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.02-2.39). Results were similar when restricted to those without evidence of chronic kidney disease (estimated glomerular filtration rate ≥60 mL·min-1·1.73 m-2) (OR 1.49, 95% CI 1.08-2.06). In an exploratory analysis, the association between B2M and thrombotic stroke was similar to the overall ischemic stroke results, but no association was observed for embolic stroke risk. CONCLUSION High levels of B2M were associated with an increased risk of ischemic stroke among women.
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Affiliation(s)
- Pamela M Rist
- From the Division of Preventive Medicine (P.M.R, M.C.J., K.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; and Department of Epidemiology (P.M.R.), Harvard T.H. Chan School of Public Health, Boston, MA.
| | - Monik C Jiménez
- From the Division of Preventive Medicine (P.M.R, M.C.J., K.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; and Department of Epidemiology (P.M.R.), Harvard T.H. Chan School of Public Health, Boston, MA
| | - Kathryn M Rexrode
- From the Division of Preventive Medicine (P.M.R, M.C.J., K.M.R.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; and Department of Epidemiology (P.M.R.), Harvard T.H. Chan School of Public Health, Boston, MA
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50
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Wu H, Lee L, Wang W. Associations among Serum Beta 2 Microglobulin, Malnutrition, Inflammation, and Advanced Cardiovascular Event in Patients with Chronic Kidney Disease. J Clin Lab Anal 2017; 31:e22056. [PMID: 27645611 PMCID: PMC6817072 DOI: 10.1002/jcla.22056] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2016] [Accepted: 07/28/2016] [Indexed: 11/10/2022] Open
Abstract
OBJECTIVES This study examines the associations among serum β2 microglobulin (B2M), malnutrition, inflammation, and atherosclerosis (MIA) in those with chronic kidney disease (CKD). METHODS CKD patients who were followed in Taoyuan General Hospital from 2009 to 2015 were enrolled. Demographic and biochemical data, including B2M and C-reactive protein (CRP) were reviewed. The participants were stratified according to B2M tertiles. Adjusted hazard ratios (AHRs) and cumulative survival curves for death and MIA syndrome were evaluated by Cox hazard model and Kaplan-Meier method. We also calculated the area under the curve for the receiver operating characteristic curve (AUROC). RESULTS From a total of 312 CKD patients, mean follow-up time was 39.7 months. Compared to those with lowest tertile of B2M, the highest tertile group had lower serum albumin, hemoglobin, and estimated glomerular filtration rate. After multivariate adjustment, the associations among tertiles of B2M, death or dialysis, cardiovascular events (CVEs), and MIA syndrome remained significant. The AHRs for the highest tertile group in death or dialysis, CVEs, and MIA syndrome were 25.91 and 65.84 and 152.50(all Ps <0.05).The AUROC for B2M in death or dialysis, CVEs, and MIA syndrome were greater than that for creatinine. The best cut-off value of B2M for predicting death or dialysis, CVEs, and MIA syndrome were 5.39 mg/dL(sensitivity: 67.1%, specificity 62.5%), 4.21 mg/dL(sensitivity: 85.1%, specificity 52.1%), and 5.40 mg/dL(sensitivity: 79.7%, specificity 64.1%). CONCLUSIONS In those with CKD, serum B2M was more sensitive than creatinine in predicting CVEs and MIA syndrome.
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Affiliation(s)
- Hung‐Chieh Wu
- Division of NephrologyDepartment of Internal MedicineTaoyuan General HospitalMinistry of Health and WelfareTaoyuanTaiwan
| | - Lin‐Chien Lee
- Department of Physical Medicine and RehabilitationCheng Hsin General HospitalTaipeiTaiwan
| | - Wei‐Jie Wang
- Department of Biomedical EngineeringChung Yuan Christian UniversityTaoyuanTaiwan
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