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20-羟二十碳四烯酸是心血管疾病的潜在治疗靶点。

20-Hydroxyeicosatetraenoic acid is a potential therapeutic target in cardiovascular diseases.

机构信息

Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Curr Drug Metab. 2013 Jul;14(6):706-19. doi: 10.2174/1389200211314060007.

Abstract

Arachidonic acid (AA) is metabolized by enzymes of the cytochrome P450 (CYP) 4A and CYP4F subfamilies to 20- hydroxyeicosatetraeonic acid (20-HETE), which plays an important role in the cardiovascular system. In the current work, we reviewed the formation of 20-HETE in different species by different CYPs; 20-HETE metabolism by cyclooxygenases (COXs) and different isomerases; and the current available inducers and inhibitors of 20-HETE formation in addition to its agonists and antagonists. Moreover we reviewed the negative role of 20-HETE in cardiac hypertrophy, cardiotoxicity, diabetic cardiomyopathy, and in ischemia/reperfusion (I/R) injury. Lastly, we reviewed the role of 20-HETE in different hypertension models such as the renin/angiotensin II model, Goldblatt model, spontaneously hypertensive rat model, androgen-induced model, slat- and deoxycorticosterone acetate (DOCA)-salt-induced models, and high fat diet model. 20-HETE can affect pro- and anti-hypertensive mechanisms dependent upon where, when, and by which isoform it has been produced. In contrast to hypertension we also reviewed the role of 20-HETE in endotoxin-induced hypotension and the natriuretic effects of 20-HETE. Based on the recent studies, 20-HETE production and/or action might be a therapeutic target to protect against the initiation and progression of cardiovascular diseases.

摘要

花生四烯酸 (AA) 可被细胞色素 P450 (CYP) 4A 和 CYP4F 亚家族的酶代谢为 20-羟二十碳四烯酸 (20-HETE),后者在心血管系统中发挥重要作用。在当前的工作中,我们综述了不同 CYP 在不同物种中生成 20-HETE 的情况;20-HETE 经环加氧酶 (COX) 和不同异构酶的代谢;以及 20-HETE 生成的现有诱导剂和抑制剂,以及其激动剂和拮抗剂。此外,我们还综述了 20-HETE 在心脏肥大、心肌毒性、糖尿病心肌病和缺血/再灌注 (I/R) 损伤中的负面作用。最后,我们综述了 20-HETE 在不同高血压模型中的作用,如肾素/血管紧张素 II 模型、Goldblatt 模型、自发性高血压大鼠模型、雄激素诱导模型、盐和脱氧皮质酮醋酸盐 (DOCA)-盐诱导模型以及高脂肪饮食模型。20-HETE 可以影响促高血压和抗高血压机制,具体取决于其产生的位置、时间和同工型。与高血压相反,我们还综述了 20-HETE 在内毒素性低血压和 20-HETE 的利钠作用中的作用。基于最近的研究,20-HETE 的产生和/或作用可能是一种治疗靶点,可用于预防心血管疾病的发生和进展。

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