Abstract 15570: DHA and EPA Differentially Modulate the Inflammatory Response Following Myocardial Infarction in Obese and Aging Mice
Increased linoleic acid intake from a safflower oil (SO) high diet increases coronary heart disease risk, and this effect is blunted by a diet rich in fish oil (FO). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two FO components, but their individual contributions to the cardioprotective effects have not been elucidated. We determined DHA and EPA effects on remodeling of the left ventricle (LV) following myocardial infarction (MI) in an obesity superimposed on aging model, to assess the hypothesis that DHA, but not EPA, would attenuate the post-MI inflammatory response. C57BL/6J male mice were fed a 10% (w/w) SO diet for 3 months, beginning at 12 months of age, to induce obesity. At 15 months of age, the obese mice were randomized to no treatment or 5% (w/w) EPA or DHA isocaloric diets for 2 months (n=15/group). At 17 months of age, the 3 groups of mice were subjected to MI and evaluated at day (d)1 post-MI and compared to d0 no-MI diet only controls. At d0, SO showed increased plasma interferon gamma-induced protein-10 (IP-10), leukemia inhibitory factor-1 (LIF-1), lymphotactin, and VCAM-1 levels, concomitant with increased LV collagen accumulation (all p<0.05). DHA or EPA both inhibited these effects. Post-MI, d1 survival was similar among MI groups, and infarct areas ranged from 40±2 to 46±3% for the 3 groups (p=0.57). End diastolic dimensions increased in all 3 groups compared to the respective d0 controls (all p<0.05). Compared to SO d1 post-MI, both EPA or DHA MI groups showed decreased plasma levels of interleukin (IL)-18 and macrophage derived chemokine (MDC), as well as reduced neutrophil infiltration into the infarcted area (all p<0.05). DHA, but not EPA, also decreased LIF-1 and macrophage chemoattractant protein-5 (both p<0.05), suggesting that macrophage trafficking may be reduced by DHA. In conclusion, SO contributes to post-MI inflammation that is differentially attenuated by DHA or EPA.
- © 2013 by American Heart Association, Inc.