Decreased circulating catestatin levels are associated with coronary artery disease: The emerging anti-inflammatory role
Decreased circulating catestatin levels are associated with coronary artery disease: The emerging anti-inflammatory role
复制标题
循环中儿茶素水平降低与冠状动脉疾病相关：新兴的抗炎作用。
DOI：
10.1016/j.atherosclerosis.2018.12.025
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发表时间：
2019-02-01
期刊：
影响因子：
5.3
通讯作者：
Jin, Wei
中科院分区：
文献类型：
--
作者：
Chen, Yanjia;Wang, Xiaoqun;Jin, Wei
背景和目标：神经肽catestatin（CST）是一种内源性烟碱胆碱能拮抗剂，具有多效性心脏保护激素的作用。本研究旨在探讨CST与冠状动脉疾病（coronary artery disease，CAD）的相关性及其可能机制，方法与结果：比较224例CAD患者和204例健康对照者血清CST浓度，并分析921例CAD患者血清CST浓度与动脉粥样硬化程度的关系。与健康受试者相比，CAD患者的血清CST浓度较低[ 1.14（1.05-1.24）ng/mL vs. 2.15（1.92-2.39）ng/mL，p < 0.001]，且与疾病严重程度呈负相关（r=-0.208，p < 0.001）。在培养的内皮细胞中，CST通过激活血管紧张素转换酶2（ACE 2）抑制TNF-α诱导的炎性细胞因子和粘附分子的表达。CST的管理减少了白细胞-内皮细胞的相互作用，在体外和体内，并减弱了动脉粥样硬化的ApoE（-/-）小鼠喂养高脂肪饮食的发展。CST的这些保护作用可被ACE 2抑制剂阻断。结论：冠心病患者血清CST浓度较低，且与动脉粥样硬化严重程度呈负相关。CST是一种新型的抗动脉粥样硬化肽，通过ACE 2依赖性机制抑制炎症反应和EC-白细胞相互作用。
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-alpha-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.