Genetic Insufficiency of 12/15LOX in Mice‐Facilitated Angiogenic Response Post‐Myocardial Infarction

Abstract

12/15 lipoxygenase (12/15LOX) is a fat‐metabolizing enzyme that uses different fatty acids to form bioactive lipids in pathology of diseases such as myocardial infarction (MI)‐induced heart failure (HF). 12/15LOX‐null mice show an effective healing pattern with a higher survival rate as compared to wildtype (WT), but the mechanism is unknown. We aimed to test whether 12/15LOX expression in wildtype mice impairs angiogenesis of infarcted myocardium post‐MI in acute and chronic HF. MI was surgically induced in wildtype (WT; C57BL/6) and 12/15LOX‐null mice (2–4 months old) by ligating the left anterior descending artery. Mice LV tissues were stained using biotinylated Griffonia (Bandeiraea) Simplicifolia Lectin at acute (day; d1 and d5) and chronic (d28 and d56) time points suggestive of chronic HF post‐MI. To determine angiogenesis, LV 40X images of the remote and peri‐infarct regions were analyzed using light microscopy and then quantified blood vessel density (BVD). As expected, non‐MI naive controls (d0) had the largest BVD compared to remote and peri‐infarct regions of WT and 12/15LOX‐deficient mice post‐MI. BVD diminished in WT and 12/15LOX‐deficient mice at d1. In the remote region, 12/15LOX‐deficient mice had a higher BVD than WT on d5, d28 and d56. BVD peaked on d5 for 12/15LOX‐deficient mice and on d28 for WT. In the peri‐infarct region, 12/15LOX‐deficient mice showed higher BVD than WT on days 1, 5, 28 and 56. BVD peaked on d5 in 12/15LOX‐deficient and WT mice post‐MI. BVD data indicated that angiogenesis peaks on day 5 (during the acute phase) in 12/15LOX‐deficient mice as compared to WT post‐MI. In summary, the presented results suggest that 12/15LOX delay angiogenesis post‐MI in HF.Support or Funding InformationThis research was supported in part by the American Physiology Society to MC as a STRIDE fellow and a grant from the National Heart, Lung and Blood Institute to GVH (HL132989).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.