Overexpression of CuZnSOD in coronary vascular cells attenuates myocardial ischemia/reperfusion injury

• Published in: Free radical biology & medicine 2000-10, Vol.29 (7), p.589-596
• Main Authors: Chen, Zhongyi, Oberley, Terry D, Ho, Ye-Shih, Chua, Chu Chang, Siu, Brian, Hamdy, Ronald C, Epstein, Charles J, Chua, Balvin H.L
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Catalase - metabolism; Coronary Vessels - enzymology; Coronary Vessels - pathology; Endothelium, Vascular - enzymology; Endothelium, Vascular - pathology; Free radicals; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Heart ischemia/reperfusion injury; Heat-Shock Proteins - metabolism; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins - metabolism; Humans; In Vitro Techniques; L-Lactate Dehydrogenase - analysis; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - pathology; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - enzymology; Myocardium - metabolism; Neoplasm Proteins - metabolism; RNA, Messenger - genetics; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Transcription, Genetic; Transgenic mice; Zn superoxide dismutase
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(00)00363-4

Superoxide dismutase scavenges oxygen radicals, which have been implicated in ischemia/reperfusion (I/R) injury in the heart. Our experiments were designed to study the effect of a moderate increase of copper/zinc superoxide dismutase (CuZnSOD) on myocardial I/R injury in TgN(SOD1)3Cje transgenic mice. A species of 0.8 kb human CuZnSOD mRNA was expressed, and a 273% increase in CuZnSOD activity was detected in the hearts of transgenic mice with no changes in the activities of other antioxidant enzymes. Furthermore, immunoblot analysis revealed no changes in the levels of HSP-70 or HSP-25 levels. Immunocytochemical study indicated that there was increased labeling of CuZnSOD in the cytosolic fractions of both endothelial cells and smooth muscle 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 as heart rate × LVDP, was 48 ± 3% in the transgenic hearts as compared to 30 ± 5% in the nontransgenic hearts ( p < .05). The improved cardiac function was accompanied by a significant reduction in lactate dehydrogenase release from the transgenic hearts. Our results demonstrate that overexpression of CuZnSOD in coronary vascular cells renders the heart more resistant to I/R injury.