title: Linoleic acid attenuates cardioprotection induced by resolvin D1.
abstract: We previously observed that resolvin D1 (RvD1), a metabolite of the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid, reduces infarct size by a mechanism involving the PI3-K/Akt pathway. In parallel, the beneficial effect of a high omega-3 PUFA diet on infarct size can be attenuated by increased omega-6 PUFA consumption. The present study was designed to determine if augmented linoleic acid (LA), an omega-6 PUFA administered at the same time, attenuates the cardioprotective action of RvD1. Male Sprague-Dawley rats received 0.1μg RvD1 alone or with one of three LA doses (1, 5 or 10μg) directly into the left ventricle chamber 5min before ischemia. The animals underwent 40min of ischemia by occlusion of the left descending coronary artery followed by 30min or 24h of reperfusion. Infarct size and neutrophil accumulation were evaluated after 24h of reperfusion, while caspase-3, -8 and -9 and Akt activities were assessed at 30min of reperfusion. LA attenuated cardioprotection afforded by RvD1, resulting in significantly increased infarct size. Neutrophil accumulation and Akt activity were similar between groups. Caspase activities, especially caspase-9, which could be activated by ischemia, were stimulated in the presence of LA, suggesting that this omega-6 PUFA accentuates ischemia intensity. The present results indicate that LA significantly attenuates the beneficial effect of RvD1 on infarct size. Therefore, reduction of omega-6 intake should be considered to maintain the protection afforded by RvD1.
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: 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: 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. Electronic address: guy.rousseau@umontreal.ca.
authors.forename: Guy
authors.initials: G
authors.lastname: Rousseau
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D019787:Linoleic Acid / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002316:Cardiotonic Agents; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D019787:Linoleic Acid; D020169:Caspases
keywords: Linoleic acid; Myocardial infarction; Omega-3; Omega-6; Resolvin D1