RGMa参与粥样斑块中血管平滑肌细胞表型转化的影像分析及机制研究

血管平滑肌细胞（VSMC）表型转化是影响粥样斑块易损性的重要因素，进而影响缺血性卒中发病风险。研究显示多种神经导向分子参与斑块形成机制，影响斑块的易损性。RGMa作为一种功能多样的神经导向分子，其是否影响斑块易损性尚无定论。既往研究显示Slug作为近来发现的VSMC表型转化诱导因子受RhoA等小G蛋白及TGF-β1/Smad通路的激活调控。我们推测在斑块形成中应激活化的RGMa相关小G蛋白通路及协同激活的TGF-β1/Smad通路通过调控重要转录因子Slug，促进VSMC表型转化，影响斑块易损性。我们拟通过(1)动物模型及细胞水平研究：分析干预RGMa对斑块形成的影响，进一步探索RGMa参与其中VSMC表型转化的作用方式。(2)临床研究：分析急性AS相关缺血性脑卒中患者血浆RGMa、相关功能性SNP与多模态MR头颈动脉斑块的影像特征、临床特征的关系，以期为AS相关卒中预防与治疗提供新思路。

Phenotypic transformation of vascular smooth muscle cells is an important factor affecting the vulnerability of atherosclerotic plaques and thus the risk of ischemic stroke. Studies have shown that a variety of neural guidance molecules are involved in the mechanism of atherosclerosis formation and affect the vulnerability of plaques. Whether RGMa, as a neural guidance molecule with diverse functions, affects plaque vulnerability has not been studied. Previous studies have shown that Slug, as a recently discovered inducer of phenotype transformation of VSMC, is regulated by activation of RhoA and other small G proteins and TGF-β1/Smad pathway. We hypothesized that the stress-activated RGMa-related small G protein pathway and the synergistically activated TGF-β1/Smad pathway promote VSMC phenotypic transformation and affect plaque vulnerability by regulating transcription factor Slug in plaque formation. We intend to (1)analyze whether intervention of RGMa-related pathways can regulate atherosclerotic plaque formation, and further explore the role of RGMa-related signaling pathways in VSMC phenotypic transformation in atherosclerotic plaques, (2)analyze the relationship between plasma RGMa, RGMa-related functional SNP and clinical features、imaging characteristics of multimodal MR plaque imaging in patients with acute atherosclerosis-related ischemic stroke. This study is intended to provide new ideas for the prevention and treatment of atherosclerosis-related ischemic stroke.