Abstract 211: Relative Protection By Cardiac Specific And Leukocyte Heme Oxygenase-1 (HO-1) In Myocardial Ischemia-reperfusion
Enhanced production of reactive oxygen species plays a deleterious role in myocardial injury following ischemia-reperfusion. Heme oxygenase-1 (HO-1) is a heme catabolizing enzyme that is induced by and acts against oxidant-induced tissue injury. Recent studies have suggested that there is a cardioprotective effect of HO-1 against ischemia-reperfusion injury. However, the role of HO-1 on blood cells against ischemia-reperfusion injury versus that in cardiac tissue itself, is unknown. The purpose of this study was to elucidate the role of HO-1 in the heart or blood cells against myocardial ischemia-reperfusion injury. We designed a series of bone marrow reconstitutions between HO-1−/− and HO-1+/+ mice. After 8 weeks, myocardial ischemia-reperfusion injury was elicited in each group of mice. The left anterior descending coronary artery was occluded for 45 min, followed by 1 d of reperfusion. The infarct size in HO-1+/+ mice reconstituted with HO-1−/− marrow was significantly increased compared with HO-1+/+ mice reconstituted with HO-1+/+ marrow (62% vs. 51%; P < 0.05; n = 4). However, there was no difference of infarct size between HO-1−/− mice reconstituted with HO-1−/− marrow and HO-1−/− mice reconstituted with HO-1+/+ marrow (73.9% vs. 72.5%; n = 4). The NADPH oxidase activity and the intensity of nitrotyrosine in ischemic myocardium from HO-1+/+ mice reconstituted with HO-1−/− marrow were significantly increased compared with HO-1+/+ mice reconstituted with HO-1+/+ marrow (by 161% and 123%, respectively; P < 0.05). However, the NADPH oxidase activity and the intensity of nitrotyrosine in ischemic myocardium were almost identical between between HO-1−/− mice reconstituted with HO-1−/− marrow and HO-1−/− mice reconstituted with HO-1+/+ marrow. These results suggest that HO-1 confers cardioprotection by suppressing oxidative damage, and HO-1 in the heart has stronger cardioprotective effect against myocardial-ischemia reperfusion compared with HO-1 on circulating blood cells.