Overexpression of CuZnSOD in coronary vascular cells attenuates myocardialischemia/reperfusion injury

Superoxide dismutase scavenges oxygen radicals, which have been implicated in ischemia/reperfusion (I/R) injury in the heart. Our experiments were des igned to study the effect of a moderate increase of copper/zinc superoxide dismutase (CuZnSOD) on myocardial I/R injury in TgN(SOD1)3Cje transgenic mi ce. A species of 0.8 kb human CuZnSOD mRNA was expressed, and a 273% increa se in CuZnSOD activity was detected in the hearts of transgenic mice with n o changes in the activities of other antioxidant enzymes. Furthermore, immu noblot analysis revealed no changes in the levels of HSP-70 or HSP-25 level s. Immunocytochemical study indicated that there was increased labeling of CuZnSOD in the cytosolic fractions of both endothelial cells and smooth mus cle cells, but not in the myocytes of the hearts from transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed a s heart rate x LVDP, was 48 +/- 3% in the transgenic hearts as compared to 30 +/- 5% in the nontransgenic hearts (p < .05). The improved cardiac funct ion was accompanied by a significant reduction in lactate dehydrogenase rel ease from the transgenic hearts. Our results demonstrate that overexpressio n of CuZnSOD in coronary vascular cells renders the heart more resistant to I/R injury. (C) 2000 Elsevier Science Inc.