The apelin-APJ system in heart failure pathophysiologic relevance and therapeutic potential
The apelin-APJ system in heart failure pathophysiologic relevance and therapeutic potential
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DOI：
10.1016/j.bcp.2007.12.015
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发表时间：
2008-05-15
影响因子：
5.8
通讯作者：
Newby, David E.
中科院分区：
文献类型：
--
作者：
Japp, Alan G.;Newby, David E.
Apelin是先前孤立的G蛋白偶联受体APJ的内源性配体。这种新的肽信号通路在心脏和血管系统中广泛存在，并且正在成为心血管稳态的重要调节因子。在临床前模型中，在心脏正常和衰竭的大鼠中，apelin引起一氧化氮依赖性血管扩张，减少心室前负荷和后负荷，并增加心脏收缩力。Apelin-APJ信号还能减轻缺血性心肌损伤，维持衰老和慢性压力过载时的心脏功能。apelin和APJ表达的下调与心脏功能下降相吻合，这增加了apelin-APJ活性降低可能具有病理生理意义的可能性。目前，人体研究数据有限，但慢性心力衰竭患者apelin和APJ表达的变化与临床前模型相似。现在需要详细的临床研究来确定apelin在人类心血管生理和病理生理中的作用，并确定增强apelin信号传导在心力衰竭患者中的治疗潜力。(C) 2008爱思唯尔公司版权所有。
Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor, APJ. This novel peptidic signalling pathway is widely represented in the heart and vasculature, and is emerging as an important regulator of cardiovascular homeostasis. In preclinical models, apelin causes nitric oxide-dependent vasodilatation, reduces ventricular preload and afterload, and increases cardiac contractility in rats with normal and failing hearts. Apelin-APJ signalling also attenuates ischemic myocardial injury and maintains cardiac performance in ageing and chronic pressure overload. Downregulation of apelin and APJ expression coincides with declining cardiac performance raising the possibility that diminished apelin-APJ activity may have pathophysiologic implications. At present, data from human studies is limited but changes in apelin and APJ expression in patients with chronic heart failure parallel those seen in preclinical models. Detailed clinical investigation is now required to establish the role of apelin in human cardiovascular physiology and pathophysiology, and to determine the therapeutic potential of augmenting apelin signalling in patients with heart failure. (C) 2008 Elsevier Inc. All rights reserved.