1. Causal role of circulating inflammatory cytokines in cardiac diseases, structure and function.
- Author
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Ruan, Weiqiang, Zhou, Xiaoqin, Liu, Huizhen, Wang, Ting, Zhang, Guiying, and Lin, Ke
- Abstract
• Hepatocyte growth factor (HGF) causally increases risk of ischemic and overall stroke. • Programmed cell death 1 ligand 1 (PD-L1) has a protective causal effect against atrial fibrillation. • Several inflammatory cytokines, including CCL20, CDCP1, Flt3L and IL-10RA, are causally associated with increased coronary artery disease risk. • Interleukin-4 (IL-4) and leukemia inhibitory factor receptor (LIF-R) levels are causally related to changes in right ventricular and right atrial structure and function, respectively. Inflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research. We conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data. Outcomes included coronary artery disease, myocardial infarction, stroke, atrial fibrillation, heart failure, abdominal aortic aneurysm, deep vein thrombosis of lower extremities, pulmonary embolism, cardiac structure and functional parameters. Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied. Hepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; P = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; P = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; P = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes. Our MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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