Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics.

Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics.
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DOI:
10.1016/j.pharmthera.2009.02.009
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发表时间:
2009-06
影响因子:
13.5
通讯作者:
Kass, David A.
Kass, David A.
中科院分区:
医学1区
文献类型:
--
作者:
Tsai, Emily J.;Kass, David A.

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环鸟苷3′,5 ′-一磷酸(cGMP)介导心血管系统内多种细胞类型的广泛生理过程。在级联反应的任何一步-- cGMP合成、效应物激活或catalysts--的功能障碍信号传导与许多心血管疾病有关,从高血压到动脉粥样硬化到心脏肥大和心力衰竭。在这篇综述中,我们概述了cGMP信号级联的每一步,并讨论其在心血管系统内的调节和生理作用。此外,我们说明了cGMP信号如何在特定的心血管疾病状态下变得失调。cGMP在心脏生理学和病理生理学中的普遍作用为cGMP信号在心血管疾病治疗中的药理学调节提供了巨大的机会。我们详细介绍了已经开发或正在开发的各种治疗干预策略,总结了相关的临床前和临床研究。
Cyclic guanosine 3′,5′-monophosphate (cGMP) mediates a wide spectrum of physiologic processes in multiple cell types within the cardiovascular system. Dysfunctional signaling at any step of the cascade--- cGMP synthesis, effector activation, or catabolism--- have been implicated in numerous cardiovascular diseases, ranging from hypertension to atherosclerosis to cardiac hypertrophy and heart failure. In this review, we outline each step of the cGMP signaling cascade and discuss its regulation and physiologic effects within the cardiovascular system. In addition, we illustrate how cGMP signaling becomes dysregulated in specific cardiovascular disease states. The ubiquitous role cGMP plays in cardiac physiology and pathophysiology presents great opportunities for pharmacologic modulation of the cGMP signal in the treatment of cardiovascular diseases. We detail the various therapeutic interventional strategies that have been developed or are in development, summarizing relevant preclinical and clinical studies.
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