Abstract 13276: DHA but not Etanercept Expedites Resolution of Inflammation leading to Improved Survival Following Myocardial Infarction in Aging Mice
Dietary intake of n-3 polyunsaturated fatty acids (PUFA) has been touted for cardioprotective benefits. n-3 PUFA contains docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) but their individual effects on left ventricle (LV) remodeling remains unclear compared to anti-inflammatory molecule. We assessed the individual component of n-3 PUFA and their therapeutic potential on LV remodeling post-MI in aging mice (n=150). Male C57BL/6J mice were fed chow diet for first 12 months and then placed on safflower oil (SO; 10% w/w) enriched diet (n-6 PUFA) for 3 months to induce obesity. Then mice were randomized into 5 isocaloric groups: SO or DHA or EPA or DHA+EPA (D+E) or Etanercept (ETAN; 5mg/kg/day) (n=26-30 mice/group) for 2 months. At 17 months of age, mice were subjected to permanent coronary artery ligation resulting in MI and monitored for d1 and d5 survival; maintaining no-MI as d0 naïve controls. Post-MI survival was highest in DHA fed mice compared with ETAN and all other groups (p<0.05). Mice in all groups had lower fractional shortening and extensive ventricular remodeling post-MI compared to d0 control. DHA and D+E mice reduced neutrophil infiltration at d1 compared to SO (p<0.05). The DHA and EPA fed mice showed increased ccr2 and cxcl2 expression at d1 indicating the higher monocyte density, expediting the clearance of dead LV tissues. DHA and EPA groups (both p<0.05) showed early induction of resolving enzyme HO-1 (hemeoxygenase) at d1 which peaked at d5 facilitating resolution of inflammation post-MI. LV immunohistochemistry of DHA fed mice showed enhanced expression of COX-2 (cyclooxygenase-2) at d1 and 5-LOX (5-lipoxygenase) at d5 post-MI compared to d0, and other 4 groups (all p<0.05). Further, DHA fed mice showed the higher expression of timp-1, timp-2 and timp-3 with decrease in MMP-9 levels at d5 stabilizing the matrix maturation within the infarcted LV and thus promoting resolution. In summary, our results suggest that DHA but not ETAN improved post-MI survival in aging and obese mice by reducing neutrophil density, via coordination of COX, LOX and HO-1, leading to enhanced resolution of inflammation post-MI.
Author Disclosures: K.A. Ingle: None. V. Kain: None. G.V. Halade: Research Grant; Significant; NIH-NCCAM R00AT006704 to GVH.
- © 2014 by American Heart Association, Inc.