随年龄增长体细胞增殖能力下降，血管系统却出现平滑肌反常增殖。我们前期研究发现内皮Jag1降低是老龄反向调节血管内皮衰老和平滑肌增殖的重要原因，可能与其调节内皮分泌IGFBP1/ADAM19/CXCL1蛋白有关。以此为基础进一步提出科学假设：老龄时Jag1表达减少导致血管内皮分泌功能失衡，以Jag1为靶标的分泌蛋白IGFBP1/ADAM19/CXCL1间发挥协同和交互作用，进一步通过调节细胞衰老和增殖途径导致血管不良修复。分别建立血管内皮Jag1条件敲除和野生型老年小鼠颈动脉损伤模型，阐明筛选分泌蛋白水平与血管病变和老龄的关系；建立内皮-平滑肌共培养体系，通过基因获得或缺失、GST-pull down、质谱分析等方法分析分泌蛋白在调节内皮衰老和平滑肌增殖中的协同及交互机制，并从与经典细胞衰老增殖机制的关系探讨其分子机制。本研究旨在阐明血管修复过程中内皮再生和平滑肌增殖矛盾的关键问题。

Generally the proliferative potential of somatic cells decreases along with aging. The vascular wall, however, displays over-activity of smooth muscle cells (SMC) proliferation. Our previous findings showed the bidirectional regulation of Jag1 on endothelial cells (EC) senescence and SMC proliferation during aging process, which was possibly mediated by the soluble proteins including IGFBP1/ADAM19/CXCL1. We therefore hypothesized that the decreased Jag1 expression with aging results in the imbalanced paracrine of EC, and the soluble proteins which targeted to Jag1 exert synergetic and reciprocal regulations, and further mediated the abnormal vascular repair by regulating the classical senescence and proliferative pathways. By using the carotid artery injury model from the endothelial Jag1 conditional knockout mice and wild type aging mice, this study was designed to observe the dynamic expression pattern of the target paracrine proteins as well as its relation with the vascular lesions. In the EC-SMC co-culture system, the gene synergetic and molecular reciprocal regulations were studied by using methods involving loss or gain of gene function, GST-pull down and mass spectrometric analysis. Finally, the molecular mechanisms will be investigated to clarify its relationship with the classical vascular senescence and proliferative pathways. This study was hopeful to address the key point of vascular EC regeneration and SMC proliferation in vascular repair.