Myocardial G protein-coupled receptor kinases: implications for heart failure therapy.

G Iaccarino, R J Lefkowitz, W J Koch
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引用次数: 34

Abstract

The beta-adrenergic signaling cascade is an important regulator of myocardial function. Significant alterations of this pathway are associated with several cardiovascular diseases, including congestive heart failure (CHF). Included in these alterations is increased activity and expression of G protein-coupled receptor kinases (GRKs), such as the beta-adrenergic receptor kinase (beta ARK1), which phosphorylate and desensitize beta-adrenergic receptors (beta ARs). A body of evidence is accumulating that suggests that GRKs, in particular beta ARK1, are critical determinants of cardiac function under normal conditions and in disease states. Transgenic mice with myocardial-targeted alterations of GRK activity have shown profound changes in the in vivo functional performance of the heart. Included in these studies is the compelling finding that inhibition of beta ARK1 activity or expression significantly enhances cardiac function and potentiates beta AR signaling in failing cardiomyocytes. This article summarizes the advances made in the study of beta ARK1 in the heart and addresses its potential as a novel therapeutic target for CHF.

心肌G蛋白偶联受体激酶:对心力衰竭治疗的影响。
肾上腺素能信号级联是心肌功能的重要调节因子。该通路的显著改变与几种心血管疾病有关,包括充血性心力衰竭(CHF)。这些变化包括G蛋白偶联受体激酶(GRKs)的活性和表达增加,如β -肾上腺素能受体激酶(β ARK1),其磷酸化和脱敏β -肾上腺素能受体(β ARs)。越来越多的证据表明,在正常情况和疾病状态下,grk,特别是β - ARK1,是心脏功能的关键决定因素。心肌靶向改变GRK活性的转基因小鼠在体内的心脏功能表现出了深刻的变化。在这些研究中有一个令人信服的发现,即抑制β ARK1活性或表达可显著增强心功能,并增强衰竭心肌细胞中的β AR信号。本文综述了β - ARK1在心脏中的研究进展,并阐述了其作为CHF新治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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