Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice

Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon mo noxide and antioxidant bilirubin We have previously shown that in response to hypoxia, HO-1-null mice develop infarcts in the right ventricle of their hearts and that their cardiomyocytes are damaged by oxidative mess. To tes t whether HO-1 protects against oxidative injury in the heart, we generated cardiac-specific transgenic mice overexpressing different levels of HO-1. By use of a Langendorff preparation, hearts from transgenic mice showed imp roved recovery of contractile performance during reperfusion after ischemia in an HO-1 dose-dependent manner. In vivo, myocardial ischemia and reperfu sion experiments showed that infarct size was only 14.7% of the area at ris k in transgenic mice compared with 56.5% in wild-type mice. Hearts from the se transgenic animals had reduced inflammatory cell infiltration and oxidat ive damage, Our data demonstrate that overexpression of HO-1 in the cardiom yocyte protects against ischemia and reperfusion injury, thus improving the recovery of cardiac function.