First Author | Yusoff FM | Year | 2021 |
Journal | Microvasc Res | Volume | 134 |
Pages | 104126 | PubMed ID | 33373621 |
Mgi Jnum | J:305842 | Mgi Id | MGI:6706112 |
Doi | 10.1016/j.mvr.2020.104126 | Citation | Yusoff FM, et al. (2021) Bach1 plays an important role in angiogenesis through regulation of oxidative stress. Microvasc Res 134:104126 |
abstractText | 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 gamma co-activator-1alpha, 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-isoPGF2alpha 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. |