心脏干细胞外泌体源circHIPK3调控miR-29a/VEGFA促进内皮祖细胞血管新生机制的研究

新近研究表明心脏干细胞（CSCs）源外泌体（exosome）可通过传递非编码RNA（microRNAs、lncRNAs、circRNA等）在细胞与细胞之间进行信息交流，再生修复梗死心肌及血管网络。本课题组前期研究发现，缺氧预处理的心脏干细胞源exosome可促进心肌梗死区域新生血管形成，改善心肌梗死后心功能，对常氧及缺氧exosome中circRNA进行测序发现circHIPK3在缺氧预处理的exosome中显著高表达。因此，我们提出如下假设：缺氧预处理的心脏干细胞源exosome可将高表达的circHIPK3传递至血管内皮祖细胞，促进其血管新生功能，发挥改善心功能的作用，并在整体动物、细胞和分子水平全面观测心脏干细胞源exosome与内皮祖细胞的交互作用，深入研究心脏干细胞exosome源circHIPK3在表观遗传学层面影响心肌梗死后内皮祖细胞血管新生的分子机制。

Recent studies indicate that cardiac stem cell-derived exosomes ，which carry noncoding RNAs ，such as microRNAs lncRNAs、and circRNA, are critically important mediators for exchanging of information between cells.Exosomes play a vital role for regenerative infarcted myocardium and vascular network. Our previous studies showed CSC derived exosomes effetiently promote angiogenesis of cardiomyocytes, and also bioinformatics and circRNA high throughput sequencing found that circHIPK3 significantly increasing in hypoxia-exosome while compared with normal oxygen groups, So we hypothesize that hypoxia pretreatment can induces circHIPK3 increasing.circHIPK3 can be transported to insulted EPCs by exosomes, then promote the ability of EPCs angiogenesis. Our study aims at understanding the reciprocity between exoxome derived circHIPK3 and angiogenesis of EPCs and providing new molecular biomarkers for the prevention and treatment of ventricular remodeling after acute myocardial infarction.