GRK2与心肌纤维化关系的研究进展

G蛋白偶联受体激酶（G protein-coupled receptor kinases, GRK）2是一种能够脱敏多种G蛋白偶联受体（G protein-coupled receptor, GPCR）的激酶，心肌GRK2能够抑制GPCRs成员之一—β肾上腺素能受体（β-adrenergic receptor, β-ARs）的功能，即通过环磷酸腺苷（cAMP）终止其G蛋白介导的信号传导，减弱心肌细胞的收缩能力和肾上腺素能储备。阻断GRK2可以恢复βARs的敏感性，进而改善和逆转心肌梗死后心力衰竭。近年来，GRK2在心血管疾病中的非经典作用也已被阐述，包括胰岛素信号的负调节、线粒体调节作用以及心肌细胞存活和凋亡信号的修饰，这些新作用表明GRK2可能不依赖于其典型GPCR脱敏作用而影响心脏收缩功能、细胞代谢和生存，并促进心力衰竭。本文旨在对GRK2与心肌纤维化关系的研究进展进行回顾与总结，将国内外最新研究成果作统一阐述。

Research progress in relationship between GRK2 and myocardial fibrosis

G protein-coupled receptor kinase 2 (GRK2) is a kinase capable of desensitizing multiple G protein-coupled receptors (GPCRs). Myocardial GRK2 can inhibit the functions of β-adrenergic receptor (β-ARs), a member of GPCRs, terminating its G-protein-mediated signaling by cAMP and attenuating myocardial cell contractility and adrenergic reserve. Blocking GRK2 restores the sensitivity of β-ARs, which in turn improves and reverses heart failure after myocardial infarction. In recent years, the non-classical effects of GRK2 in cardiovascular disease have also been elucidated, including the negative regulation of insulin signaling, mitochondrial regulation, and modification of cardiomyocyte survival and apoptosis signals. These new effects suggest that GRK2 may not be dependent on its typical GPCR. Desensitization affects cardiac contractile function, cellular metabolism and survival, and promotes heart failure. This article aims to review and summarize the latest research progress in the relationship between GRK2 and myocardial fibrosis at home and abroad.