20-HETE作用受体的发现及其对高血压的影响

Discovery of 20-HETE receptor and its effects on hypertension

花生四烯酸(arachidonic acid,AA)可通过环氧合酶和脂氧合酶代谢途径生成白三烯类、前列腺素类和血栓素类等物质[1]。近年研究发现,AA经过细胞色素P450(cytochrome P450,CYP)代谢途径中的表氧化酶作用可生成环氧二十碳四烯酸(epoxyeicosatrienoic acids,EETs),经过羟化酶作用生成羟基二十碳四烯酸(hydroxyeicosatetraeonic acids,HETEs),如20-羟基二十碳四烯酸(20-hydroxyeicosatetraenoic acid,20-HETE)。

20-Hydroxyeicosatetraenoic acid(20-HETE)is a potent vasoactive eicosanoid discovered in recent years,which has multiple vascular effects including stimulation of smooth muscle contractility,migration,and proliferation,as well as endothelial cell dysfunction and inflammation.Clinical and experimental research suggests that20-HETE is an important mediator of cardiovascular function,and plays a critical role in the pathogenesis of hypertension,stroke,myocardial infarction and vascular diseases.Recently,G-protein-coupled receptor75(GPR75)was identified as a20-HETE receptor and mediated the development of20-HETE-dependent hypertension.The discovery of20-HETE-GPR75pairing provides the molecular basis for the signaling and pathophysiological functions mediated by20-HETE in hypertension and cardiovascular diseases.In this brief review,we discuss the recent findings related to the effects of20-HETE in the pathogenesis of hypertension and the discovery and effects of GPR75.