Linoleic acid attenuates cardioprotection induced by resolvin D1

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 0.1 mu g RvD1 alone or with one of three LA doses (1, 5 or 10 mu g) directly into the left ventricle chamber 5 min before ischemia. The animals underwent 40 min of ischemia by occlusion of the left descending coronary artery followed by 30 min or 24 h of reperfusion. Infarct size and neutrophil accumulation were evaluated after 24 h of reperfusion, while caspase-3,-8 and -9 and Akt activities were assessed at 30 min 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. (C) 2016 Elsevier Inc. All rights reserved.