Yanjia Chen1, Xiaoqun Wang2, Chendie Yang2, Xiuxiu Su2, Wenbo Yang3, Yang Dai3, Hui Han1, Jie Jiang2, Lin Lu1, Haibo Wang3, Qiujing Chen3, Wei Jin4. 1. Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. 2. Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. 3. Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. 4. Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China. Electronic address: jinwei1125@126.com.
Abstract
BACKGROUND AND AIMS: The neuropeptide catestatin (CST) is an endogenous nicotinic cholinergic antagonist that acts as pleiotropic cardiac protective hormone. This study investigated the association between CST and coronary artery disease (CAD) and the underlying mechanisms. METHODS AND RESULTS: The serum concentration of CST among 224 CAD patients and 204 healthy controls was compared, and its association with atherosclerosis severity in 921 CAD patients was further analyzed. Compared to healthy subjects, serum CST concentration was lower in patients with CAD [1.14 (1.05-1.24) ng/mL vs. 2.15 (1.92-2.39) ng/mL, p < 0.001] and was inversely correlated with disease severity (r = -0.208, p < 0.001). In cultured endothelial cells, CST suppressed TNF-α-elicited expression of inflammatory cytokines and adhesion molecules by activating angiotensin-converting enzyme-2 (ACE2). Administration of CST reduced leukocyte-endothelium interactions in vitro and in vivo, and attenuated the development of atherosclerotic in ApoE-/- mice fed a high-fat diet. These protective effects by CST were blocked by an ACE2 inhibitor. CONCLUSIONS: Serum CST concentration is lower in CAD patients and is inversely associated with the severity of atherosclerosis. CST acts as a novel anti-atherogenic peptide that inhibits inflammatory response and EC-leukocyte interactions via an ACE2-dependent mechanism.
BACKGROUND AND AIMS: The neuropeptide catestatin (CST) is an endogenous nicotinic cholinergic antagonist that acts as pleiotropic cardiac protective hormone. This study investigated the association between CST and coronary artery disease (CAD) and the underlying mechanisms. METHODS AND RESULTS: The serum concentration of CST among 224 CADpatients and 204 healthy controls was compared, and its association with atherosclerosis severity in 921 CADpatients was further analyzed. Compared to healthy subjects, serum CST concentration was lower in patients with CAD [1.14 (1.05-1.24) ng/mL vs. 2.15 (1.92-2.39) ng/mL, p < 0.001] and was inversely correlated with disease severity (r = -0.208, p < 0.001). In cultured endothelial cells, CST suppressed TNF-α-elicited expression of inflammatory cytokines and adhesion molecules by activating angiotensin-converting enzyme-2 (ACE2). Administration of CST reduced leukocyte-endothelium interactions in vitro and in vivo, and attenuated the development of atherosclerotic in ApoE-/- mice fed a high-fat diet. These protective effects by CST were blocked by an ACE2 inhibitor. CONCLUSIONS: Serum CST concentration is lower in CADpatients and is inversely associated with the severity of atherosclerosis. CST acts as a novel anti-atherogenic peptide that inhibits inflammatory response and EC-leukocyte interactions via an ACE2-dependent mechanism.
Authors: Pamela González-Dávila; Markus Schwalbe; Arpit Danewalia; René Wardenaar; Boushra Dalile; Kristin Verbeke; Sushil K Mahata; Sahar El Aidy Journal: Gut Microbes Date: 2022 Jan-Dec