β-Adrenergic receptor, an essential target in cardiovascular diseases
β-Adrenergic receptor, an essential target in cardiovascular diseases
复制标题
DOI：
10.1007/s10741-019-09825-x
复制
发表时间：
2020-03-01
影响因子：
4.6
通讯作者：
Li Changxing
中科院分区：
文献类型：
--
作者：
Ali, Daniel Chikere;Naveed, Muhammad;Li Changxing
β-肾上腺素能受体(β-AR)属于细胞表面受体大家族，称为G蛋白偶联受体(GPCRs)。它们与Gs蛋白(GαS)偶联，激活腺苷环化酶(AC)，产生环状AMP((C)AMP)，从而提供有价值的反应，影响心功能，如损伤。激动剂与βAR的结合增强了构象变化，导致了GαS亚型的异源三聚体G蛋白，它是细胞中激活(C)AMP的AC刺激G蛋白。然而，心血管疾病(CVD)的死亡率和β1受体的增加已被报道，而β2 AR是一种很有前途的工具，可以通过信号转导改善心血管系统(CVS)的调节功能。它增加Gα水平，从而激活βAR激酶(βARK)，通过激活心肌细胞βARs来影响和促进心力衰竭(HF)的进展。我们还解释说，GRKs的增加实际上将改善HF的发病机制，这是通过β-Ars的脱敏而发生的，这导致收缩储备的丧失。儿茶酚胺的浓度或过度刺激导致脑血管疾病，如中风、心力衰竭和心肌肥厚。当儿茶酚胺反应性降低时，会导致老年人衰老，因为心肌中βAR敏感性和密度的降低加强了人心脏中β受体对AC的下调。
beta-Adrenergic receptors (beta ARs) belong to a large family of cell surface receptors known as G protein-coupled receptors (GPCRs). They are coupled to Gs protein (G alpha s) for the activation of adenylyl cyclase (AC) yielding cyclic AMP ((C)AMP), and this provides valuable responses, which can affect the cardiac function such as injury. The binding of an agonist to beta AR enhances conformation changes that lead to the G alpha s subtype of heterotrimeric G protein which is the AC stimulatory G protein for activation of (C)AMP in the cells. However, cardiovascular diseases (CVD) have been reported as having an increased rate of death and beta 1AR, and beta 2AR are a promising tool that improves the regulatory function in the cardiovascular system (CVS) via signaling. It increases the G alpha level, which activates beta AR kinase (beta ARK) that affects and enhances the progression of heart failure (HF) through the activation of cardiomyocyte beta ARs. We also explained that an increase in GPCR kinases (GRKs) would practically improve the HF pathogenesis and this occurs via the desensitization of beta ARs, which causes the loss of contractile reserve. The consistency or overstimulation of catecholamines contributes to CVD such as stroke, HF, and cardiac hypertrophy. When there is a decrease in catecholamine responsiveness, it causes aging in old people because the reduction of beta AR sensitivity and density in the myocardium enhances downregulation of beta ARs to AC in the human heart.