Oxidative stress is involved in the mechanism of atherosclerotic lesion 
formation and in the mechanisms underlying the development of other pathogenic 
conditions of the cardiovascular system, including endothelial dysfunction, 
hypertension, and heart failure. Reducing oxidative stress may be a reasonable 
therapeutic approach to treat cardiovascular diseases. HO-1 is a cytoprotective 
enzyme that is induced in response to oxidative stress and degrades heme into 
carbon monoxide (CO) and bilirubin, both of which have cytoprotective effects. A 
substantial body of evidence suggests that introduction of HO-1, either 
pharmacologically or by a gene delivery technique, confers cytoprotection in 
ischemic heart disease and atherosclerosis in animals. Recent studies have 
revealed that CO has anti-inflammatory properties and that administration of CO 
provides protection against atherosclerosis and ischemic heart disease. 
Discovery of Bach1, a transcriptional repressor of HO-1, has greatly contributed 
to the understanding of the regulation of HO-11 expression, providing a clue to 
a development of alternative method to enhance HO activity. Bach1 normally 
represses HO-1 expression. However, upon exposure to oxidative stress, Bach1 
loses its repressive activity and is exported out of the nucleus, which in turn 
results in the upregulation of HO-1. Bach1 knockout mice, expressing an 
increased amount of HO-1, are resistant to pro-atherosclerotic and ischemic 
stresses. These findings indicate that inhibition of Bach1 may be a novel 
approach to enhance protection against stress. In summary, the Bach1-HO-1 system 
is an important defense mechanism against oxidative stress. Development of a 
safe and effective method to enhance this pathway, such as Bach1 inhibitor, may 
be of great clinical relevance.