Endogenous nitric oxide synthase inhibitors in the biology of disease: markers, mediators, and regulators?
Endogenous nitric oxide synthase inhibitors in the biology of disease: markers, mediators, and regulators?
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DOI：
10.1161/atvbaha.112.247726
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Leiper J
中科院分区：
文献类型：
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作者：
Caplin B;Leiper J
不对称甲基精氨酸通过与l -精氨酸竞争一氧化氮合酶活性位点抑制体内一氧化氮合成。不对称二甲基精氨酸的高循环水平预示着不良后果，特别是血管事件，但现在有越来越多的实验和流行病学证据表明，这些分子和调节这一途径的酶在心血管疾病中起着机制作用。最近的数据提供了这些氨基酸水平改变对人类和啮齿动物的影响，然而这些报告也表明，仅基于测量和/或调节循环不对称二甲基精氨酸的简单方法是不够的。本文将概述内源性甲基精氨酸的基本生物化学和生理学，研究其在疾病发病机制中的作用的实验和观察证据，并研究这些分子的治疗调节潜力。
The asymmetric methylarginines inhibit nitric oxide synthesis in vivo by competing with L-arginine at the active site of nitric oxide synthase. High circulating levels of asymmetric dimethylarginine predict adverse outcomes, specifically vascular events but there is now increasing experimental and epidemiological evidence that these molecules, and the enzymes that regulate this pathway, play a mechanistic role in cardiovascular diseases. Recent data have provided insight into the impact of altered levels of these amino-acids in both humans and rodents, however these reports also suggest a simplistic approach based on measuring and/or modulating circulating asymmetric dimethylarginine alone is inadequate. This review will outline the basic biochemistry and physiology of endogenous methylarginines, examine both the experimental and observational evidence for a role in disease pathogenesis and examine the potential for therapeutic regulation of these molecules.