title: Metabolites derived from omega-3 polyunsaturated fatty acids are important for cardioprotection.
abstract: Although controversial, some data suggest that omega-3 polyunsaturated fatty acids (PUFA) are beneficial to cardiovascular diseases, and could reduce infarct size. In parallel, we have reported that the administration of Resolvin D1 (RvD1), a metabolite of docosahexaenoic acid, an omega-3 PUFA, can reduce infarct size. The present study was designed to determine if the inhibition of two important enzymes involved in the formation of RvD1 from omega-3 PUFA could reduce the cardioprotective effect of omega-3 PUFA. Sprague-Dawley rats were fed with a diet rich in omega-3 PUFA during 10 days before myocardial infarction (MI). Two days before MI, rats received a daily dose of Meloxicam, an inhibitor of cyclooxygenase-2, PD146176, an inhibitor of 15-lipoxygenase, both inhibitors or vehicle. MI was induced by the occlusion of the left coronary artery for 40min followed by reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion while caspase-3, -8 and Akt activities were assessed at 30min of reperfusion. Rats receiving inhibitors, alone or in combination, showed a larger infarct size than those receiving omega-3 PUFA alone. Caspase-3 and -8 activities are higher in ischemic areas with inhibitors while Akt activity is diminished in groups treated with inhibitors. Moreover, the study showed that RvD1 restores cardioprotection when added to the inhibitors. Results from this study indicate that the inhibition of the metabolism of Omega-3 PUFA attenuate their cardioprotective properties. Then, resolvins seem to be an important mediator in the cardioprotection conferred by omega-3 PUFA in our experimental model of MI.
authors.affiliation: Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5; Département de pharmacologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Kim
authors.initials: K
authors.lastname: Gilbert
authors.affiliation: Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5; Département de pharmacologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Mandy
authors.initials: M
authors.lastname: Malick
authors.affiliation: Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5; Département de pharmacologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Ness
authors.initials: N
authors.lastname: Madingou
authors.affiliation: Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5; Département de pharmacologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Charles
authors.initials: C
authors.lastname: Touchette
authors.affiliation: Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5; Département de pharmacologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bourque-Riel
authors.affiliation: Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5; Département de pharmacologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: Leandro
authors.initials: L
authors.lastname: Tomaro
authors.affiliation: Centre de biomédecine, Hôpital du Sacré-Cœur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5; Département de pharmacologie, Université de Montréal, C.P. 6128 Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7. Electronic address: guy.rousseau@umontreal.ca.
authors.forename: Guy
authors.initials: G
authors.lastname: Rousseau
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004032:Diet / Q000009:adverse effects; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; D052246:Cyclooxygenase 2 Inhibitors; D015525:Fatty Acids, Omega-3; D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053181:Caspase 8
keywords: Cardioprotection; Inhibitors; Metabolites; Myocardial infarction; Omega-3; Resolvin D1