The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development.
The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development.
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DOI：
10.1016/j.phrs.2016.05.008
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发表时间：
2016-08
影响因子：
9.3
通讯作者：
Koch WJ
中科院分区：
文献类型：
--
作者：
Hullmann J;Traynham CJ;Coleman RC;Koch WJ
心力衰竭（HF）是一种全球性流行病，在目前研究的任何疾病中死亡率和发病率最高。G蛋白偶联受体（GPCR）是心血管功能的重要调节因子。激活的GPCR在称为“脱敏”的过程中被GPCR激酶（GRK）“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年里，GRK2和GRK5都被证明是发生在衰竭心脏中的分子改变的关键介质。在本综述中，我们将强调最近的研究结果，进一步表征“非经典”GRK信号在HF中观察到。此外，我们还将提出潜在的治疗策略（即小分子抑制，microRNA，基因治疗），可能有潜力在打击HF GRKs的有害影响。
Heart failure (HF) is a global epidemic with the highest degree of mortality and morbidity of any disease presently studied. G protein-coupled receptors (GPCRs) are prominent regulators of cardiovascular function. Activated GPCRs are “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, both GRK2 and GRK5 have been demonstrated to be critical mediators of the molecular alterations that occur in the failing heart. In the present review, we will highlight recent findings that further characterize "non-canonical" GRK signaling observed in HF. Further, we will also present potential therapeutic strategies (i.e. small molecule inhibition, microRNAs, gene therapy) that may have potential in combating the deleterious effects of GRKs in HF.