"Canonical and non-canonical actions of GRK5 in the heart".
"Canonical and non-canonical actions of GRK5 in the heart".
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DOI：
10.1016/j.yjmcc.2016.01.027
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发表时间：
2016-03
影响因子：
5
通讯作者：
Koch WJ
中科院分区：
文献类型：
--
作者：
Traynham CJ;Hullmann J;Koch WJ
随着世界范围内平均寿命的持续增加，心力衰竭（HF）的发病率急剧增加，导致目前研究的任何疾病的最高程度的死亡率和发病率。G蛋白偶联受体（GPCRs）在心血管功能的调节中起着重要作用。GPCR在称为“脱敏”的过程中被GPCR激酶（GRK）有效地“关闭”。GRKs 2和5在心脏中高度表达，并且已知在HF中上调。在过去的20年中，GRK2在HF中的作用已经被广泛研究。然而，直到最近，GRK5在心脏病理生理学中的作用尚未阐明。在本综述中，我们将重点介绍GRK5在正常生理状态下心肌中的作用，以及其在HF进展中的明显关键作用。此外，我们还将提出潜在的治疗策略（即小分子抑制，基因治疗），可能有潜力在打击HF GRK5的有害影响。
As the average world-wide lifespan continues to increase, heart failure (HF) has dramatically increased in incidence leading to the highest degree of mortality and morbidity of any disease presently studied. G protein-coupled receptors (GPCRs) play a prominent role in regulation of cardiovascular function. GPCRs are effectively “turned off” by GPCR kinases (GRKs) in a process known as “desensitization”. GRKs 2 and 5 are highly expressed in the heart, and known to be upregulated in HF. Over the last 20 years, the role of GRK2 in HF has been widely studied. However, until recently, the role of GRK5 in cardiac pathophysiology had yet to be elucidated. In the present review, we will focus on GRK5’s role in the myocardium in normal physiology, and its apparent critical role in the progression of HF. Further, we will also present potential therapeutic strategies (i.e. small molecule inhibition, gene therapy) that may have potential in combating the deleterious effects of GRK5 in HF.