颈动脉支架植入术已逐渐成为治疗严重颈动脉狭窄的常见治疗方法之一，然而支架植入后再狭窄严重影响患者远期疗效，新生内膜增生为其主要病理改变，但其机制不清。我们前期通过多种动物模型的基因测序，筛选到Sema4D在血管损伤后表达增加。本项目拟采用基因敲除小鼠、免疫荧光、细胞增殖、迁移、Co-IP、ChIP等体内外实验来阐明Sema4D，一方面，可促进平滑肌细胞PlexinB1/PLCγ1复合物形成，进一步激活Rac1-GTP酶，抑制MRTFA/SRF复合物的形成，从而抑制SRF的转录活性，导致平滑肌细胞发生表型转化；另一方面，Sema4D/PlexinB1信号能够通过增加内皮细胞SP1转录因子的表达，促进内皮PDGFB基因转录，从而促使发生表型转化的平滑肌细胞趋化形成新生内膜增生。本项目的研究结果将为血管新生内膜增生提供了新的发生发展机制，为未来颈动脉支架植入后再狭窄提供新的防治靶点和理论依据。

Carotid artery stenting has gradually become one of the common treatments for severe carotid stenosis. However, restenosis after stent implantation seriously affects the long-term efficacy of patients. Neointimal hyperplasia is the main pathological procress of restenosis, but the underlying mechanisms remain elusive. We performed gene sequence of various vascular injury models and screened Sema4D as one of the most noticeably increased genes. This project intends to use knockout mice, immunofluorescence, cell proliferation, migration, Co-IP, ChIP and other in vivo and in vitro experiments to clarify: Sema4D, On the one hand, it can promote the formation of PlexinB1 / PLCγ1 complex in smooth muscle cells and further activate Rac1-GTP enzyme that inhibit the formation of MRTFA / SRF complexes, thereby inhibiting the transcriptional activity of SRF, leading to phenotype switch of smooth muscle cells; on the other hand, Sema4D / PlexinB1 signaling can promote the transcription of endothelial PDGFB gene by increasing expression of SP1 transcription factors. Thus, the smooth muscle cells undergoing phenotypic transformation are chemotactic by endothelial PDGFB to form neointimal hyperplasia. The research results of this project will provide a new mechanism for the occurrence and development of vascular neointimal thickening, and provide new targets and theoretical basis for prevention and treatment of restenosis after carotid artery stenting in the future.