Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease

ESC Heart Failure

Michael H. Olsen¹  Olle Melander²  Amra Jujić²  John Molvin²  Peter M. Nilsson²  Martin Magnusson²  Lennart Råstam²  Margrét Leósdóttir²  Manan Pareek³  Ulf Lindblad⁴  Bledar Daka⁴ 

[1] Centre for Individualized Medicine in Arterial Diseases (CIMA) University of Southern Denmark Odense Denmark;Department of Clinical Sciences Lund University, Clinical Research Center Inga Marie Nilssons gata 47 Malmö 20502 Sweden;Department of Internal Medicine Yale New Haven Hospital, Yale University School of Medicine New Haven CT USA;Institute of Medicine, Department of Public Health and Community Medicine, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden;

关键词: Cardiometabolic disease;    Cardiovascular disease;    Cathepsin D;    Diabetes;    Galectin‐4;    Proteomics;   

DOI  :  10.1002/ehf2.13036

来源: DOAJ

【 摘 要 】

Abstract Aims The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality. Methods and results Plasma samples from 1713 individuals from the Swedish population‐based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid‐binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin‐like growth factor‐binding protein 2 (IGFB2), cathepsin D (CTSD), galectin‐4 (GAL4), and paraoxonase‐3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all‐cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni‐corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17–1.41), CTSD (1.15–1.37), CD163 (1.09–1.30), IGFBP2 (1.05–1.30), and FABP4 (1.04–1.29)] and ACM and four proteins [GAL4 (1.38–1.56), CTSD (1.14–1.43), CD163 (1.09–1.36), and IGFBP2 (1.03–1.35)] with CVM. Three proteins [GAL4 (1.14–1.57), CTSD (1.12–1.50), and FABP4 (1.05–1.55)] were significantly associated with incident CE and two [GAL4 (1.03–1.54) and CTSD (1.01–1.46)] were associated with incident HF after adjusting for traditional risk factors including N‐terminal pro‐brain natriuretic peptide. Conclusions In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.

【 授权许可】

Unknown