动脉粥样硬化（AS）是缺血性脑卒中的主要病理基础。近年，连接黏附分子-A（JAM-A）在AS中的作用受到重视，其通过与配体LFA-1结合促进单核细胞迁移，并参与bFGF诱导血管新生，与AS斑块形成、不稳定密切相关。然而，目前还缺乏针对JAM-A的干预措施。我们前期工作及相关研究发现miR-145可靶向抑制JAM-A，但miR-145在血浆中易分解，如何使其稳定到达靶细胞发挥作用亟待解决。本项目提出修饰间充质干细胞外泌体抑制JAM-A抗AS假说，以外泌体作为载体运输高表达miR-145，靶向抑制JAM-A合成，并对外泌体进一步修饰，高表达JAM-Ap，并转染bFGF-siRNA质粒，分别阻断JAM-A与LFA-1的结合及抑制bFGF诱导的MAPK/ERK通路激活，从而抑制炎性细胞浸润和血管新生，稳定斑块；同时动物实验评价上述修饰对颈AS病理过程和结局的影响。本项目为有效干预颈AS提供新策略。

Atherosclerosis (AS) is the main pathological basis of ischemic stroke. Recently, the role of junctional adhesion molecule A(JAM-A) has been attentioned in AS. JAM-A can promote monocyte migration and infiltration by binding to its ligand of lymphocyte function associated antigen-A(LFA-1), and plays an important role in the endothelial migration and angiogenesis induced by basic fibroblast growth factor (bFGF), which are closely related to the formation and instability of atherosclerotic plaques. However, there is no targeted intervention for JAM-A currently. Our previous related studies have found that miR-145 can inhibit JAM-A by targeted regulation. However, miR-145 is easy to decompose in plasma and difficult to reach the target cells stably. In this project, we proposed the hypothesis that mesenchymal stem cells-derived exosomes (MSC-Exo) can inhibit JAM-A to resist atherosclerosis. MSC-Exo will be used as carriers to transport the highly expressed miR-145 and to target the inhibition synthesis of JAM-A. Meanwhile, we will also overexpress JAM-A inhibitory peptide (JAM-Ap) in MSC-Exo to block JAM-A binding to LFA-1, and transfect with bFGF-siRNA plasmids to inhibit bFGF-induced MAPK/ERK pathway activation, which can inhibit inflammatory cell infiltration, angiogenesis and stabilizing plaques by further modifying MSC-Exo. We will also evaluate the effects of the above modifications on the pathological process and outcome of cervical atherosclerosis. This project will provide new and effective strategies to intervene the formation and stability of carotid atherosclerosis.