动脉粥样硬化斑块内血管新生是斑块易损性的重要标志之一。将抑制斑块内血管新生与促进已生成的血管成熟化有机结合已经成为稳定动脉粥样硬化易损斑块新策略。近来研究发现，内皮细胞R-Ras信号通路上调后可以促进病理状况下生成的血管成熟化，但在动脉粥样硬化血管疾病领域中相关研究甚少。因此，申请人提出假说，上调动脉粥样硬化斑块新生血管内皮细胞内R-Ras信号通路可以促进血管成熟化，从而达到稳定斑块的目的。本课题将利用分子克隆技术和慢病毒包装技术将靶向动脉粥样硬化斑块内皮细胞的的多肽序列GAPGPSKSC克隆到外泌体表面富集蛋白Lamp2b上，通过电穿孔技术将R-Ras 38V质粒装载入靶向外泌体内，将其精准运输至斑块内皮细胞中。从分子、细胞及动物整体水平不同层面探讨R-Ras对斑块内血管成熟化的调控作用并阐明其机制。本研究将为预防动脉粥样硬化血管病急性事件发生提供新的治疗思路。

Atherosclerosis (AS) disease, under the influence of various vulnerable factors, eventually leads to the formation and rupture of plaques. In this process, the quantity and permeability of plaque neovascularization are the key factors. Therefore, the regulation of angiogenesis has become a therapeutic strategy for AS disease in recent years. However, there are some limitations only by inhibiting the development of new blood vessels, and how to promote the maturation of neovascular in the plaque will become a new way to stabilize the vulnerable plaque of AS. To realize the therapeutic potential of R-Ras, efficient, tissue-specific and nonimmunogenic delivery technologies must be developed. Here we will show that engineered exosomes can deliver R-Ras to atherosclerotic lesion endothelium, and the gain of function of R-Ras in endothelial cells can improve maturation of neovascular in the AS plaque.