The translational therapeutics of prostaglandin inhibition in atherothrombosis
The translational therapeutics of prostaglandin inhibition in atherothrombosis
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DOI：
10.1111/j.1538-7836.2009.03439.x
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发表时间：
2009-07-01
影响因子：
10.4
通讯作者：
Fitzgerald, G. A.
中科院分区：
文献类型：
--
作者：
Yu, Y.;Ricciotti, E.;Fitzgerald, G. A.
前列腺素是环氧合酶（考克斯）的产物，可促进和抑制动脉粥样硬化血栓形成。虽然选择性抑制考克斯-2的非甾体抗炎药（NSAID）容易导致心肌梗死、心力衰竭、高血压和中风，但抑制考克斯-1的产物，例如血栓烷（Tx）A（2），是低剂量阿司匹林的心脏保护作用的基础。来自临床药理学、啮齿动物模型、人类遗传学、观察性研究和随机试验的数据提供了对抑制考克斯产物合成或功能的影响的深入了解。许多证据为NSAID的心血管（CV）危害提供了机制解释。使用多样化的方法来阐明该途径的生物学也与理解底物再转移的影响有关，所述底物再转移是在抑制COX下游的酶（例如微粒体PGE合酶（mPGES）-1）之后进行的，并且结合D前列腺素类拮抗剂与烟酸来减弱面部潮红。
Prostaglandins, products of the cyclo-oxygenase (COX) enzymes, can both promote and restrain atherothrombosis. While non-steroidal anti-inflammatory drugs (NSAIDs) selective for inhibition of COX-2 predispose to myocardial infarction, heart failure, hypertension and stroke, suppression of products of COX-1, such as thromboxane (Tx) A(2), underlie cardioprotection from low-dose aspirin. Data from clinical pharmacology, rodent models, human genetics, observational studies and randomized trials provide insight into the implications of inhibiting COX product synthesis or function. Many lines of evidence afford a mechanistic explanation for the cardiovascular (CV) hazard from NSAIDs. Elucidation of the biology of this pathway using diversified approaches is also relevant to understanding the implications of substrate rediversion following inhibition of enzymes downstream of COXs, such as the microsomal PGE synthase (mPGES)-1 and of combining D prostanoid antagonism with niacin to attenuate facial flushing.