衰老心肌血管新生能力减弱限制了治疗性血管新生在老年缺血性心脏病(IHD)人群中的应用。我们前期研究提示生长停滞特异性蛋白6（Gas6）可促进老龄小鼠缺血心肌血管新生。通过高通量测序与生物信息学分析等预实验我们发现Gas6可通过Axl/PI3K/Akt通路显著上调lncRNA H19，后者可显著上调促进血管新生的血管新生抑制蛋白2（VASH2），而miR-6751可削弱此效应。据此假设：Gas6通过Axl/PI3K/Akt上调lncRNA H19，后者与miR-6751结合通过ceRNA机制间接上调VASH2，从而促进血管新生。本项目拟研究心肌缺血患者临床样本，构建各年龄代基因敲除心梗大鼠模型，利用荧光素酶检测、AGO2-RIP等技术，从人体、器官、细胞水平阐明Gas6调控lncRNA H19/miR-6751/VASH2促进衰老缺血心肌血管新生的作用及机制，为老年IHD提供新的治疗靶点。

The impairment of angiogenesis in aging tissues can limit the application of therapeutic angiogenesis which aims at promoting the development of new microvessels in the elderly patients who suffer from ischemic heart diseases (IHD). Our previous study indicated that Growth arrest-specific protein 6 (Gas6) promoted angiogenesis in senescent ischemic myocardium via the PI3K/Akt signaling pathway. In this study, the results from high-throughput sequencing showed that Gas6 significantly up-regulated lncRNA H19. Based on bioinformatics analysis and molecular biology experiments, we also found lncRNA H19 could significantly up-regulate vasohibin 2 (VASH2), a key mediator for the formation of new capillary. Meanwhile, miR-6751 could block the above process. Accordingly, we put forward hypotheses: Gas6 promotes senescent ischemic myocardial angiogenesis by activation of lncRNA H19 through the Axl/PI3K/Akt signaling pathway; lncRNA H19 competitively binds to miR-6751 and up-regulates VASH2, via ceRNA mechanisms. Based on our preliminary experiments, the next step of this project will focus on exploring the correlation among Gas6 and H19/miR-6751/VASH2 signaling in the regulation of angiogenesis and cardiac function of ischemic myocardium by means of luciferase assay, AGO2-RIP, clinical specimen analysis and myocardial infarction models of gene knockout rat in different age groups. This study will provide new strategies and novel targets for the prevention and treatment of IHD in the elderly.