Bach1 plays an important role in angiogenesis through regulation of oxidative stress

Farina Mohamad Yusoff, Tatsuya Maruhashi, Ki ichiro Kawano, Ayumu Nakashima, Kazuaki Chayama, Satoshi Tashiro, Kazuhiko Igarashi, Yukihito Higashi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number104126
JournalMicrovascular Research
Volume134
DOIs
Publication statusPublished - 2021 Mar

Keywords

  • Angiogenesis
  • Bach1
  • Heme oxygenase-1
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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