Bach1 is a known transcriptional repressor of the heme oxygenase-1 (HO-1) gene. The purpose of this study was to determine whether angiogenesis is accelerated by genetic ablation of Bach1 in a mouse ischemic hindlimb model. Hindlimb ischemia was surgically induced in wild-type (WT) mice, Bach1-deficient (Bach1^-/-) mice, apolipoprotein E-deficient (ApoE^-/-) mice, and Bach1/ApoE double-knockout (Bach1^-/-/ApoE^-/-) mice. Blood flow recovery after hindlimb ischemia showed significant improvement in Bach1^-/- mice compared with that in WT mice. Bach1^-/-/ApoE^-/- mice showed significantly improved blood flow recovery compared with that in ApoE^-/- mice to the level of that in WT mice. Migration of endothelial cells in ApoE^-/- mice was significantly decreased compared with that in WT mice. Migration of endothelial cells significantly increased in Bach1^-/-/ApoE^-/- mice compared with that in ApoE^-/- mice to the level of that in WT mice. The expression levels of HO-1, peroxisome proliferator-activated receptor γ co-activator-1α, angiopoietin 1, and fibroblast growth factor 2 in endothelial cells isolated from Bach1^-/-/ApoE^-/- mice were significantly higher than those in ApoE^-/- mice. Oxidative stress assessed by anti-acrolein antibody staining in ischemic tissues and urinary 8-isoPGF2α excretion were significantly increased in ApoE^-/- mice compared with those in WT and Bach1^-/- mice. Oxidative stress was reduced in Bach1^-/-/ApoE^-/- mice compared with that in ApoE^-/- mice. These findings suggest that genetic ablation of Bach1 plays an important role in ischemia-induced angiogenesis under the condition of increased oxidative stress. Bach1 could be a potential therapeutic target to reduce oxidative stress and potentially improve angiogenesis for patients with peripheral arterial disease.

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