Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis.
Heme oxygenase (HO)-1 converts heme to bilirubin, carbon monoxide, and iron. Our prior work has suggested a cardioprotective role for HO-1 in heart failure. To test whether HO-1 (heat shock protein 32) prevents cardiomyocyte apoptosis and cardiac dysfunction after ischemia-reperfusion (I/R), we generated transgenic mice overexpressing HO-1 in the heart under the control of the alpha-myosin heavy chain promoter. HO-1 transcript and protein increased markedly in the heart only. In an isolated heart preparation, we observed an enhanced functional recovery during reperfusion after ischemia in the transgenic hearts compared with nontransgenic controls. I/R injury was also performed in intact animals by coronary ligation and reperfusion to assess the protective role of HO-1 overexpression on heart apoptosis. HO-1 overexpression reduced cardiac apoptosis, as evidenced by fewer terminal deoxynucleodidyl transferase-mediated dUTP nick-end labeling-positive or in situ oligo ligation-positive myocytes, compared with nontransgenic mice. Our results indicate that cardioselective overexpression of HO-1 exerts a cardioprotective effect after myocardial I/R in mice, and this effect is probably mediated via an antiapoptotic action of HO-1.
Vulapalli
Sreesatya Raju
SR
Cardiology Unit, Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA. raju_vulapalli@urmc.rochester.edu
Chen
Zhongyi
Z
Chua
Balvin H L
BH
Wang
Tingchung
T
Liang
Chang-Seng
CS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology*; D010477:Perfusion; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse