BDNF-TrkB通路衰老改变致年老心脏血管新生及心梗再生功能下降的调控机理及干预研究

在前期原创发现：衰老使心脏微血管内皮细胞（CMECs）传导BDNF信号由年青时使用“BDNF-TrkB-FL-PI3K/AKT通路”，而在年老是使用“BDNF-TrkB-T1-Willin-Hippo通路”，该衰老表型不利于年老心脏的血管新生及梗死心肌再生的基础上，进一步研究：①BDNF在年青CMECs与其全长型受体结合，使用“BDNF-TrkB-FL-PI3K/AKT通路促进血管新生与BDNF在年老CMECs与其缺失型受体结合，使用“BDNF-TrkB-T1-Willin-Hippo通路”促进血管新生的效能与相应机理；②年青与年老心梗心脏分别实施过表达BDNF的全长型受体（TrkB-FL）及缺失型受体（TrkB-T1）干预后，是否有利于梗死心肌的再生。项目预期能为 “年老心脏血管新生功能下降”和“心脏衰老”带来源头创新的新机理，也能为治疗年老梗死心肌带来新的靶点与疗法。

In previous studies, we demonstrate that aging incurs cardiac microvascular endothelial cells (CMECs) in young heart applies BDNF-TrkB-FL-PI3K/AKT pathway to transduce the BDNF mediated angiogenesis, however, it is replaced by BDNF-TrkB-T1-Willin-Hippo pathway in old CMECs. This aging phenotype is potential damge for angiogenesis of aged heart and regeneration of aged myocardial infarction (MI). The present project is therefore designed to explore: ① Investigation of efficiency and mechanism between BDNF-TrkB-FL-PI3K/AKT pathway mediated angiogenesis in young CMECs and BDNF-TrkB-T1-Willin-Hippo pathway mdediated angiogenesis in old CMECs; ② Investigation of the intervention strategy of TrkB-FL and TrkB-T1 respectively in young and aged hearts to document whether it has beneficial effects for regeneration of aged MI. The findings of present study will reveal novel mechanism for “dysfunction of angiogenesis in aged heart” and “heart aging” as well as provide novel interventional targets for regeneration of aged MI.