Abstract 13756: Genetic Ablation of Bach1 Plays an Important Role in Angiogenesis in A Mouse Hindlimb Ischemia Model through Increases in Expression of PGC-1α and Angiopoietin 1
Background: Recent studies have shown that Bach1 downregulates the expression of heme oxygenase-1 (HO-1). HO-1 degrades heme into carbon monoxide, ferrous iron and biliverdin, which were known as antioxidants. The purpose of this study was to evaluate the role of Bach1/HO-1 pathway in ischemia-induced angiogenesis in Bach1 knockout (KO) mice.
Methods and Results: Femoral artery was ligated in C57BL/6J (WT) mice, Bach1 KO mice, apolipoprotein E (apoE) KO mice and Bach1/apoE double KO mice proximal to its superficial and deep branches. Blood flow was determined by laser Dopplar perfusion imaging. Ischemic and non -ischemic limb perfusion was measured before surgery, 3 days, 7days, and 14days after surgery. All mice were sacrificed on 14 days after surgery. Capillary density was calculated by CD31 positive cells. The number of apoptotic cells was counted by TUNEL positive cells. The migration of endothelial cells, which were isolated from each types of mice, was assessed by VEGF stimulation. The expression of angiogenic cytokines and transcriptional factors in cultured endothelial cells and each samples were performed by Western blot analysis. At 14 days after surgery, Bach1 KO mice had a greater blood perfusion index and higher capillary density compared to the WT mice (p<0.05). The number of endothelial cells migration in Bach1 KO mice was larger than that of WT mice (p<0.05). The expression of PGC-1α and angiopoietin 1 in cultured endothelial cells, were greater in Bach1 KO mice than in the WT, apoE KO and Bach1/apoE double KO mice.
Conclusion: These findings suggest that genetic ablation of Bach1 plays an important role in ischemia-induced angiogenesis through the increases in expression of PGC-1α and angiopoietin 1.
- © 2012 by American Heart Association, Inc.