Barau Caroline, Ghaleh Bijan, Berdeaux Alain, Morin Didier
Inserm, U955, Equipe 03, F-94000, Créteil, France; UMR_S955, UPEC, Université Paris-Est, F-94000, Créteil, France.
Fundam Clin Pharmacol. 2015 Feb;29(1):1-9. doi: 10.1111/fcp.12087. Epub 2014 Sep 25.
Cytochromes P450 (CYP) are a large family of enzymes widely involved in hepatic drug metabolism. While most CYP are extensively expressed in the liver, some of them are also detected in the heart where they participate through arachidonic acid metabolism to a variety of eicosanoids synthesis with different cardiovascular effects. Studies performed in the last years reported that several isoenzymes of microsomal CYP (i.e. CYP 2J2, CYP 2C8, CYP 2C9, CYP 4F) can play a role in the pathogenesis of ischemia-reperfusion. Moreover, various data indicate that microsomal CYP could represent a relevant target to develop pharmacological therapies to attenuate ischemia-reperfusion injury in the heart. As mitochondria appear to play a central role during ischemia-reperfusion, mitochondrial CYP, mainly involved in steroid hormone biosynthesis, could also become potential therapeutic target for cardioprotective strategies. Indeed, CYP 11A1 and CYP 27A1 could contribute to the preservation of the mitochondrial integrity by limiting the formation and enhancing elimination of toxic oxysterols. Further studies are required to explore whether modulation of these mitochondrial CYP could really produce cardioprotection in the human heart.
细胞色素P450（CYP）是一大类广泛参与肝脏药物代谢的酶。虽然大多数CYP在肝脏中广泛表达，但其中一些也在心脏中被检测到，它们通过花生四烯酸代谢参与多种具有不同心血管效应的类二十烷酸的合成。过去几年进行的研究报告称，微粒体CYP的几种同工酶（即CYP 2J2、CYP 2C8、CYP 2C9、CYP 4F）可在缺血再灌注的发病机制中发挥作用。此外，各种数据表明，微粒体CYP可能是开发减轻心脏缺血再灌注损伤的药物疗法的一个相关靶点。由于线粒体在缺血再灌注过程中似乎起着核心作用，主要参与类固醇激素生物合成的线粒体CYP也可能成为心脏保护策略的潜在治疗靶点。事实上，CYP 11A1和CYP 27A1可通过限制有毒氧甾醇的形成并增强其清除来有助于维持线粒体的完整性。需要进一步研究来探索对这些线粒体CYP的调节是否真的能在人类心脏中产生心脏保护作用。
