儿茶酚胺抑素（catestatin，CST）是一种源于嗜鉻蛋白A的多肽，能够作用于乙酰胆碱受体抑制儿茶酚胺释放。以去甲肾上腺素（Norepinephrine，NE）为主的儿茶酚胺的过度激活可引起病理性心脏重塑，包括心肌肥厚和纤维化，最终发展为心力衰竭。我们以往研究显示，患者从心功能A期向C期的进展过程中，CST水平逐渐下降，NE水平逐渐上升，同时伴随心脏重塑的加重，在大鼠心衰模型中发现了同样的现象，同时我们也证实NE可以增强氧化应激反应，引起心脏重塑。我们假设，CST通过减少NE释放及抑制氧化应激反应，减轻心肌肥厚和纤维化。本课题分别在体外培养的心脏细胞、整体大鼠NE心脏重塑模型中，探讨过表达CST、敲低CST表达水平对心脏重塑的影响，并针对CST抑制心脏重塑的上下游调控机制展开研究，明确CST在抑制心脏重塑中的作用，实现从临床现象的观察到基础机制的探索，为心力衰竭的防治提供新的思路和策略

Catestatin (CST), a chromogranin A (Chga)-derived peptide, inhibits release of catecholamine by acting on neuronal nicotinic acetylcholine receptor. Catecholamines, including norepinephrine(NE) mainly, whose excessive activation can cause pathological cardiac remodeling, including left ventricular hypertrophy and myocardial fibrosis, may ultimately lead to heart failure. Our previous studies have shown that the CST level decreased and the NE level increased gradually during the progression of stage A to C. The same phenomenon has been found in the rat model of heart failure. It has been proven that NE can enhance oxidative stress, which led to cardiac remodeling. We hypothesize that CST prevents the developing of cardiac hypertrophy and fibrosis via inhibiting the release of NE, reducing oxidative stress in order to improve the cardiac function. This project offers an opportunity to address the role of CST on inhibiting cardiac remodeling. We will overexpress CST or downregulate its expression in the hyperplasia cardiac fibroblasts and rats cardiac remodeling model induced by NE to identify the mechanisms of cardiac remodeling and the related regulating pathway. It may provide new ideas and strategies for the prevention and treatment of heart failure.