血管内皮损伤后修复有助于维持血管的稳态。我们前期研究表明，转录因子Bach1抑制人血管内皮细胞增殖、迁移和小鼠下肢缺血后血管新生。近期实验发现，Bach1在小鼠股动脉损伤后新生内膜中高表达，在人血管内皮细胞上Bach1与SIN3A/HDAC1转录复合物结合，抑制VEGF的表达。但是Bach1是否影响血管损伤后再内皮化，SIN3A/HDAC1转录复合物是否参与该过程尚不清楚。本课题拟在人脐静脉内皮细胞和小鼠原代血管内皮细胞上，研究Bach1是否通过招募SIN3A/HDAC1复合物结合在VEGF基因启动子区，减少VEGF基因增强子H3K27乙酰化，进而抑制VEGF表达和内皮细胞的增殖和迁移；在内皮特异的Bach1敲除小鼠股动脉内皮剥脱模型上，研究Bach1对血管损伤后再内皮化的影响和机制。这项研究将阐明Bach1调控血管内皮损伤修复的分子机制，为以Bach1为靶点治疗血管疾病提供理论依据。

Endothelial repair contributes to maintain the vascular homeostasis. We have shown that the transcription factor BTB and CNC homology 1 (Bach1) inhibited the endothelial cell proliferation and migration in human umbilical vein endothelial cells (HUVECs) and suppressed angiogenesis in mice with surgically induced hind-limb ischemia (HLI). Recently, we found that Bach1 was highly expressed in neointima after femoral artery injury in mice, and Bach1 bound to SIN3A/HDAC1 complex and suppressed vascualr endothelial growth factor (VEGF) expression in HUVECs. However, the role of Bach1 in re-endothelialization after vascular injury and whether SIN3A/HDAC1 complex is involved are largely uncharacterized. In the present study, we attempt to determine whether Bach1 inhibits the transcription of VEGF by binding to the promoter of VEGF and recruiting SIN3A/HDAC1 complex to the promoter, and reducing H3K27ac in the enhancer of VEGF, and then suppressed endothelial cell proliferation and migration in HUVECs and primary mouse vascular endothelial cells. By using femoral artery injury model in tamoxifen-inducible endothelial cell-specific Bach1–/– mice, we will investigate the role and regulation mechanisms of Bach1 in the re-endothelialization after vascular injury. This study may provide the mechanisms of Bach1 in the regulation of vascular repair after vascular injury, and give the scientific basis for the treatment of vascular diseases by targeting Bach1.