The metabolic transformation of fatty acids to form oxylipids using 12/15lipoxygenase (LOX) can promote either resolving or non-resolving inflammation. However, the mechanism of how 12/15LOX interacts with PUFA (polyunsaturated fatty acids) in post-myocardial infarction (MI) healing is unclear. Here, we reported the role of 12/15LOX in post-MI cardiac remodeling in a PUFA (10% w/w, 22 Kcal) enriched environment. Wild-type (WT; C57BL/6J) and 12/15LOX null (12/15LOX−/−) male mice of 8-12-weeks age were fed PUFA-enriched diet for 1 month and subjected to permanent coronary artery ligation. Post-MI mice were monitored for the day (d)1 or until d5 along with standard diet fed MI controls. No-MI surgery mice served as naive controls. PUFA fed WT and 12/15LOX−/− mice improved ejection fraction and reduced lung edema than WT at d5 post-MI (p<0.05). Post-MI, neutrophil density was decreased in the PUFA fed WT and 12/15LOX−/− mice at d1 (P<0.05). Deletion of 12/15LOX in mice lead to increased CYP-derived bioactive lipid mediators epoxyeicosatrienoic acids (EETs) i.e. 11,12- 14,15-EpETrE, which were further enhanced by acute PUFA intake post-MI. Macrophage density was decreased in WT+PUFA and 12/15LOX−/− mice compared with their respective standard diet fed WT control at d5 post-MI. 12/15LOX−/−+PUFA mice displayed an increased expression of ccl2 and reparative macrophages markers (ym-1, mrc-1, and arg-1; all p<0.05) in the infarcted area. Further, 12/15LOX−/− mice, with or without PUFA, showed reduced collagen deposition at d5 post-MI compared to WT. In conclusion, deletion of 12/15LOX and short-term exposure of PUFA promoted leukocyte clearance, thereby limiting cardiac remodeling and promoting an effective resolution of inflammation.
- cardiac remodeling
- fatty acids
- lipid remodeling
- myocardial infarction
- Copyright © 2017, American Journal of Physiology-Heart and Circulatory Physiology