title: Cytochrome P450 and myocardial ischemia: potential pharmacological implication for cardioprotection.
abstract: 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.
authors.affiliation: Inserm, U955, Equipe 03, F-94000, Créteil, France; UMR_S955, UPEC, Université Paris-Est, F-94000, Créteil, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Barau
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
authors.forename: Alain
authors.initials: A
authors.lastname: Berdeaux
authors.forename: Didier
authors.initials: D
authors.lastname: Morin
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System
keywords: cardioprotection; cytochrome P450; heart