Bach1 is a transcriptional repressor of heme oxygenase-1 gene (Hmox-1) and 
beta-globin gene. Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme 
that degrades pro-oxidant heme to carbon monoxide (CO) and biliverdin/bilirubin, 
which are thought to mediate anti-inflammatory and anti-oxidant actions of HO-1. 
In the present study, we investigated the role of Bach1 in tissue protection 
against myocardial ischemia/reperfusion (I/R) injury in vivo using mice lacking 
the Bach1 gene (Bach1(-/-)) and wild-type (Bach1(+/+)) mice. In Bach1(-/-) mice, 
myocardial expression of HO-1 protein was constitutively up-regulated by 
3.4-fold compared to that in Bach1(+/+) mice. While myocardial I/R induced HO-1 
protein in ischemic myocytes in both strains of mice, the extent of induction 
was significantly greater in Bach1(-/-) mice than in Bach1(+/+) mice. Myocardial 
infarction was markedly reduced in size by 48.4% in Bach1(-/-) mice. 
Pretreatment of Bach1(-/-) mice with zinc-protoporphyrin, an inhibitor of HO 
activity, abolished the infarction-reducing effect of Bach1 disruption, 
indicating that reduction in the infarct size was mediated, at least in part, by 
HO-1 activity. Thus, Bach1 plays a pivotal role in setting the levels of both 
constitutive and inducible expression of HO-1 in the myocardium. Bach1 
inactivation during I/R appears to be a key mechanism controlling the activation 
level of cytoprotective program involving HO-1.