二甲基精氨酸-二甲胺水解酶在疾病中的表达和功能

Expression and Function of Dimethylarginine Dimethylaminohydrolase in Disease

非对称性-二甲基精氨酸(ADMA)抑制一氧化氮合酶(NOS),是内皮功能损伤、心血管疾病和慢性肾脏疾病的危险因素.二甲基精氨酸-二甲胺水解酶(DDAH)可以代谢ADMA,主要分为两种.DDAH-1主要分布于肾小管、肝脏,从循环中摄取ADMA;DDAH-2主要存在于血管中,分布于内皮细胞胞膜交界处及胞内颗粒、血管平滑肌细胞肌纤维及核被膜中.DDAH的表达、调节和分布均具有特异性,可以特异地调节NO的产生.本文总结了DDAH在心血管疾病和肾脏疾病导致的内皮功能受损中所起的作用.

Asymmetric（NG,NG）-dimethylarginine（ADMA）inhibits nitric oxide（NO）synthases（NOS.） ADMA is a risk factor for endothelial dysfunction,cardiovascular mortality,and progression of chronic kidney disease.Two isoforms of dimethylarginine dimethylaminohydrolase（DDAH） metabolize ADMA.DDAH-1 is the predominant isoform in the proximal tubules of the kidney and in the liver.These organs extract ADMA from the circulation.DDAH-2 is the predominant isoform in the vasculature,where it is found in endothelial cells adjacent to the cell membrane and in intracellular vesicles and in vascular smooth muscle cells among the myofibrils and the nuclear envelope.The isoform-specific distribution and regulation of DDAH expression in the kidney and blood vessels provides potential mechanisms for nephron site-specific regulation of NO production.In this review,the recent advances in the regulation and function of DDAH enzymes,their roles in the possible contribution to endothelial dysfunction in patients with cardiovascular and kidney diseases are discussed.