Bach1 plays an important role in angiogenesis through regulation of oxidative stress.
Microvasc Res
; 134: 104126, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33373621
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.
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MEDLINE
Assunto principal:
Estresse Oxidativo
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Músculo Esquelético
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Neovascularização Fisiológica
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Células Endoteliais
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Fatores de Transcrição de Zíper de Leucina Básica
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Isquemia
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article