血管重构是血管病变的病理学基础。本组研究表明，转录因子Bach1抑制人血管内皮细胞的增殖和迁移，抑制小鼠下肢缺血后血管新生。近期预实验发现，在人主动脉血管平滑肌细胞上Bach1与核染色质重构和脱乙酰酶NuRD复合体和DNA甲基转移酶3B有结合，Bach1结合在结缔组织生长因子（CTGF）基因启动子区，抑制CTGF的表达和血管平滑肌细胞的增殖。但是Bach1如何调控血管平滑肌细胞增殖和血管重构尚不清楚。本课题拟在人主动脉血管平滑肌细胞上研究Bach1是否与染色质重构蛋白NuRD复合体以及DNA甲基转移酶相互作用，表观遗传调控CTGF基因的转录，进而抑制CTGF表达和平滑肌细胞增殖；在Bach1平滑肌细胞特异性敲除小鼠股动脉血管损伤模型上，研究Bach1对血管损伤后血管重构的影响和表观遗传调控机制。这项研究将阐明Bach1调控血管重构的分子机制，为以Bach1为靶点治疗血管疾病提供理论依据。

Vascular remodeling is the pathological basis of vascular diseases. 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). In the preliminary experiment, we found that Bach1 bound to nucleosome remodeling and histone deacetylation (NuRD) complex and DNA methyltransferase 3B (DNMT3B), occupied the promoter region of connective tissue growth factor (CTGF) gene, and suppressed CTGF expression and cell proliferaton in human aortic smooth muscle cells (HASMCs). However, the mechanisms of Bach1 in the regulation of vascular smooth muscle cell proliferation and vascular remodeling are largely uncharacterized. In the present study, we attempt to determine whether Bach1 inhibits the transcription of CTGF by binding to the promoter of CTGF and recruiting NuRD complex and DNMT3B to the promoter, and then suppressed cell proliferation in HASMCs. By using femoral artery injury model in smooth muscle cell-specific Bach1 knock out mice, we will investigate the role and epigenetic mechanisms of Bach1 in the vascular remodeling after vascular injury. This study may provide the molecular mechanisms of Bach1 in the regulation of vascular remodeling, and give the scientific basis for the treatment of vascular diseases by targeting Bach1.