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

• Published in: Microvascular research Vol. 134; p. 104126
• Main Authors: Yusoff, Farina Mohamad, Maruhashi, Tatsuya, Kawano, Ki-ichiro, Nakashima, Ayumu, Chayama, Kazuaki, Tashiro, Satoshi, Igarashi, Kazuhiko, Higashi, Yukihito
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2021
• Subjects: Angiogenesis; Animals; Apoptosis; Bach1; Basic-Leucine Zipper Transcription Factors - deficiency; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - metabolism; Blood Flow Velocity; Cell Movement; Cells, Cultured; Disease Models, Animal; Endothelial Cells - metabolism; Endothelial Cells - pathology; Heme oxygenase-1; Heme Oxygenase-1 - metabolism; Hindlimb; Ischemia - genetics; Ischemia - metabolism; Ischemia - pathology; Ischemia - physiopathology; Male; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Microvascular Density; Muscle, Skeletal - blood supply; Neovascularization, Physiologic; Oxidative Stress; Regional Blood Flow; Signal Transduction; Angiogenesis; Oxidative stress; Bach1; Heme oxygenase-1
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1016/j.mvr.2020.104126

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. •Bach1 is a known transcriptional repressor of the heme oxygenase-1 (HO-1) gene.•Bach1 plays an important role in ischemia-induced angiogenesis under the condition of increased oxidative stress.•Bach1 could improve angiogenesis for patients with peripheral arterial disease through the decrease in oxidative stress.