摘要
花生四烯酸(AA)的代谢与心血管疾病的发生发展密切相关,而细胞色素P450(CYP)酶则在AA体内代谢中扮演着重要的角色。机体内的CYP表氧化酶,如CYP2C8、CYP2C9和CYP2J2可将AA转化为环氧二十碳三烯酸(EETs),而CYP4A11和CYP4F2等羟化酶则可催化AA生成羟基二十碳四烯酸(HETEs)。AA的上述两种代谢产物(尤其是EETs)可调节心血管系统并参与多种心血管疾病。CYP酶的基因多态性等遗传因素及外源性药物等环境因素可通过调节CYP酶的表达或活性影响机体内EETs和HETEs的生物合成,从而导致心血管疾病的个体差异。本文将着重介绍CYP酶介导的AA代谢在心血管疾病发生发展中发挥的重要作用,以及潜在影响因素(外源性药物和基因多态性),以期为心血管疾病的防治及机制研究等提供依据。
The metabolism of arachidonic acid（AA）is closely associated with the development of cardiovascular diseases,while cytochrome P450enzymes（CYPs）play key roles in the metabolism of AA.The main human CYP epoxygenases including CYP2C8,CYP2C9,and CYP2J2,catalyze AA to four regioisomer epoxyeicosatrienoic acids（EETs）.On the other hand,CYPω-hydroxylases such as CYP4A11and CYP4F2metabolize arachidonic acid to 20-hydroxyeicosatetraenoic acid（20-HETE）.Both EETs and HETEs exhibit a wide range of established protective effects on the human cardiovascular system.The genetic factors（such as polymorphism of CYPs）and the environmental factors（such as co-administrated with inhibitors against CYPs）could influence both the expression and the functions of the CYPs participating in AA metabolism,leading to a significant inter-individual variability in the biosynthesis of EETs or HETEs,and thus affects the development of cardiovascular diseases.This review will focus on the key roles of CYP-mediated AA metabolism in the development of cardiovascular diseases,and the potential affecting factors including gene polymorphism and xenobiotics on such biotransformation.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2017年第7期618-624,共7页
Journal of Clinical Cardiology
基金
辽宁省自然科学基金(No:2015020663)
辽宁省研究生教育教学改革研究项目(No:2016)
关键词
CYP酶
花生四烯酸代谢
外源物
基因多态性
心血管疾病
Cytochrome P450enzymes
AA metabolism
xenobiotics
gene polymorphism
cardiovascular diseases
