Bach1 is a stress-responsive transcriptional factor that is thought to control 
the expression levels of cytoprotective factors, including heme-oxygenase 
(HO)-1. In the present study, we investigated the roles of Bach1 in the 
development of left ventricular (LV) hypertrophy and remodeling induced by 
transverse aortic constriction (TAC) in vivo using Bach1 gene-deficient 
(Bach1(-/-)) mice. TAC for 3 weeks in wild-type control (Bach1(+/+)) mice 
produced LV hypertrophy and remodeling manifested by increased heart weight, 
histological findings showing increased myocyte cross-sectional area (CSA) and 
interstitial fibrosis (picro Sirius red staining), reexpressions of ANP, BNP, 
and betaMHC genes, and echocardiographic findings showing wall thickening, LV 
dilatation, and reduced LV contraction. Deletion of Bach1 caused significant 
reductions in heart weight (by 16%), CSA (by 36%), tissue collagen content (by 
38%), and gene expression levels of ANP (by 75%), BNP (by 45%), and betaMHC (by 
74%). Echocardiography revealed reduced LV dimension and ameliorated LV 
contractile function. Deletion of Bach1 in the LV caused marked upregulation of 
HO-1 protein accompanied by elevated HO activity in both basal or TAC-stimulated 
conditions. Treatment of Bach1(-/-) mice with tin-protoporphyrin, an inhibitor 
of HO, abolished the antihypertrophic and antiremodeling effects of Bach1 gene 
ablation. These results suggest that deletion of Bach1 caused upregulation of 
cytoprotective HO-1, thereby inhibiting TAC-induced LV hypertrophy and 
remodeling, at least in part, through activation of HO. Bach1 repressively 
controls myocardial HO-1 expression both in basal and stressed conditions, 
inhibition of Bach1 may be a novel therapeutic strategy to protect the 
myocardium from pressure overload.