血管重塑是动脉粥样硬化形成的病理基础。血管平滑肌细胞（VSMC）由收缩型变为增殖型的表型转化是导致血管重塑的重要原因。我们前期研究通过全转录组RNA测序发现VSMC表型转化过程中，剪接因子SRRM4及其下游靶基因Abi1剪接异构体Abi1-p的表达显著上调。Abi1-p具有额外的富脯氨酸蛋白结合域，我们推测其可能通过激活Erk1/2信号通路参与VSMC表型转化，但具体作用机制仍有待揭示。本课题拟利用分子生物学方法和生物信息学技术，在细胞以及临床样本层面，通过系统生物学研究手段，阐明SRRM4通过介导Abi1可变剪接调控VSMC表型转化的机制，并验证干预SRRM4及Abi1-p相关信号通路对调控VSMC表型转化、抑制血管重塑进而延缓动脉粥样硬化进程的关键作用，为临床治疗动脉粥样硬化提供新的作用靶点。

Vascular remolding is the pathological base of atherosclerosis. Vascular smooth muscle cell (VSMC) phenotypic switch from contractile to proliferative plays a vital role in vascular remolding. By analyzing whole transcriptome data from contractile and proliferative VSMC, we found expression of the splicing factor SRRM4 is increased in proliferative VSMC. Moreover, we also identified that an alternative splice variant of Abi1 gene, Abi1-p, is highly expressed within proliferative VSMC. Abi1-p contains an additional proline-rich region and can active Erk1/2 signaling. Therefore, we hypothesize that upregulation of SRRM4 drives phenotypic switch of VSMC. Structurally and functionally reprogramed by SRRM4, Abi1-p confers VSMC proliferative phenotype through promoting expression of proliferative markers and repressing contractile markers. In this study, we propose to use in vitro and in vivo methods to reveal the mechanism by which SRRM4 and Abi1-p drive VSMC phenotypic switch. We will also try to validate whether targeting SRRM4 and Abi1-p associated signaling can prevent VSMC phenotypic switch and vascular remolding. This study may guide the development of novel therapeutics aimed at atherosclerosis.