Vascular protective effects of cytochrome p450 epoxygenase-derived eicosanoids
Vascular protective effects of cytochrome p450 epoxygenase-derived eicosanoids
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DOI：
10.1016/j.abb.2004.10.009
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发表时间：
2005-01-15
影响因子：
3.9
通讯作者：
Liao, JK
中科院分区：
文献类型：
--
作者：
Spiecker, M;Liao, JK
细胞色素P450表氧化酶将花生四烯酸代谢为具有生物活性的类花生酸。主要的环氧化产物是顺式-环氧二十碳三烯酸（EET）的四种区域异构体，5，6-、8，9-、11，12-和14，15-EET。参与EET形成的主要环氧合酶亚型之一属于CYP 2基因家族。在人类中，P450表氧化酶CYP 2 J2在心血管系统中表达，即内皮、血管平滑肌和心肌细胞。CYP 2 J2具有血管保护作用，其包括但不限于针对缺血-再灌注损伤的保护、缺氧-再氧合后活性氧物质的抑制、促炎性转录因子、核因子-κ B（NF-κ B）的抑制、血管平滑肌迁移的减弱和纤维蛋白溶解途径的增强。尽管EET的区域异构体在不同程度上引起这些作用，但11，12-EET似乎在抗炎、抗迁移和促纤维蛋白溶解作用方面最有效。因此，CYP 2，12及其衍生的花生四烯酸代谢产物可能在正常和病理生理条件下调节血管功能中发挥重要作用。(C)2004年爱思唯尔公司All rights reserved.
Cytochrome P450 epoxygenases metabolize arachidonic acid to biologically active eicosanoids. Primary epoxidation products are four regioisomers of cis-epoxyeicosatrienoic acid (EET), 5,6-, 8 9-, 11,12-, and 14,15-EET. One of the predominant epoxygenase iso-forms involved in EET formation belongs to the CYP2 gene family. In humans, the P450 epoxygenase, CYP2J2, is expressed in the cardiovascular system, namely the endothelium, vascular smooth muscle, and cardiomyocyte. CYP2J2 possesses vascular protective effects, which include but are not limited to, protection against ischemia-reperfusion injury, Suppression of reactive oxygen species following hypoxia-reoxygenation, inhibition of the pro-inflammatory transcription factor, nuclear factor-kappaB (NF-kappaB), attenuation of vascular smooth Muscle migration, and enhancement of a fibrinolytic pathway. Although regioisomers of EET elicit these effects to varying degrees, 11,12-EET appears to be the most potent with respect to anti-inflammatory, anti-migratory, and pro-fibrinolytic effects. Thus, CYP2,12 and its derived arachidonic acid metabolites may play important roles in regulating Vascular function under normal and pathophysiological conditions. (C) 2004 Elsevier Inc. All rights reserved.