Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation.
Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation.
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DOI：
10.1016/j.yjmcc.2009.10.022
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发表时间：
2010-02
影响因子：
5
通讯作者：
Lee CR
中科院分区：
文献类型：
--
作者：
Deng Y;Theken KN;Lee CR
细胞色素P450(CYP)环氧酶催化花生四烯酸环氧化成环氧二十碳三烯酸(EETs)，再被可溶性环氧化物水解酶(SEH)迅速水解成二羟基二十碳三烯酸(DHETs)。众所周知，CYP环氧合酶来源的EETs具有强大的血管扩张作用；然而，近年来EETs的细胞效应及其对各种炎症过程的调节越来越受到重视，这表明该途径在心血管系统中的作用超出了维持血管张力的范围。特别是，CYP环氧合酶衍生的EETs通过减弱核因子-kappaB的激活抑制内皮细胞的激活和白细胞的黏附，抑制止血，保护心肌缺血再灌注损伤，并通过调节多个细胞信号通路促进内皮细胞的存活。因此，CYP环氧合酶途径是药物干预增强EETs心血管保护作用的新靶点。本文将重点介绍CYP环氧合酶途径在心血管炎症调控中的作用，1)描述CYP环氧合酶衍生的EET生物合成和sEH介导的EET水解在心血管系统关键炎症过程中的功能影响，2)讨论这一途径与心血管疾病的发病和治疗的潜在相关性，3)确定未来研究的领域。
The cytochrome P450 (CYP) epoxygenase enzymes CYP2J and CYP2C catalyze the epoxidation of arachidonic acid to epoxyeicosatrienoic acids (EETs), which are rapidly hydrolyzed to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). It is well-established that CYP epoxygenase-derived EETs possess potent vasodilatory effects; however, the cellular effects of EETs and their regulation of various inflammatory processes have become increasingly appreciated in recent years, suggesting that the role of this pathway in the cardiovascular system extends beyond the maintenance of vascular tone. In particular, CYP epoxygenase-derived EETs inhibit endothelial activation and leukocyte adhesion via attenuation of nuclear factor-kappaB activation, inhibit hemostasis, protect against myocardial ischemia-reperfusion injury, and promote endothelial cell survival via modulation of multiple cell signaling pathways. Thus, the CYP epoxygenase pathway is an emerging target for pharmacological manipulation to enhance the cardiovascular protective effects of EETs. This review will focus on the role of the CYP epoxygenase pathway in the regulation of cardiovascular inflammation, and 1) describe the functional impact of CYP epoxygenase-derived EET biosynthesis and sEH-mediated EET hydrolysis on key inflammatory process in the cardiovascular system, 2) discuss the potential relevance of this pathway to pathogenesis and treatment of cardiovascular disease, and 3) identify areas for future research.
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DOI：
10.1097/00008571-200110000-00006
发表时间：
2001-10-01
期刊：
PHARMACOGENETICS
影响因子：
--
作者：
Dai, D;Zeldin, DC;Goldstein, JA
通讯作者：
Goldstein, JA
影响因子：
4.8
作者：
Cowart, LA;Wei, SZ;Capdevila, JH
通讯作者：
Capdevila, JH
影响因子：
20.1
作者：
Campbell, WB;Gebremedhin, D;Harder, DR
通讯作者：
Harder, DR
DOI：
10.1124/jpet.105.085605
发表时间：
2005-07-01
影响因子：
3.5
作者：
Fang, X;Hu, SM;Spector, AA
通讯作者：
Spector, AA
影响因子：
8.3
作者：
Elmarakby, AA;Quigley, JE;Imig, JD
通讯作者：
Imig, JD