外体miR-25靶向KLF2/4介导内皮细胞炎症损伤在幽门螺杆菌感染诱发冠心病中的作用机制研究

The relationship between Helicobacter pylori (Hp) infection and parenteral system disease has attracted much attention. Recent studies have shown that Hp infection is a risk factor for coronary heart disease (CHD), which has become a hot spot in the field of cardiovascular. Exosomes can transfer genetic materials between cells, which is involved in signal transmission and inflammation regulation. Our previous studies have found that, the peripheral blood of atherosclerosis (AS) patients with Hp infection showed an increasement of miR-25. Exosomes from Hp-infected gastric epithelial cells showed a high expression of miR-25, which is involved in endothelial cell inflammatory injury. Furthermore, we found that KLF2/4 are both potential targets of miR-25. Our hypothesis is that: the high expression of miR-25 from Hp infected gastric epithelial cells, is transported to the vascular endothelial cells by exosomes. MiR-25 can inhibit the expression of KLF2/4, which may eventually lead to endothelial cell inflammatory injury, and accelerate the development of AS, and may eventually lead to CHD. We will interfere miR-25 expression to clarify the function; to verify KLF2/4 as target gene of miR-25; to explore the in vivo mechanism and clinical significance. Our research will provide mechanistic evidence for Hp infection involved in the pathogenesis of endothelial cell inflammation injury and highlight potential prevention and therapeutic strategies for CHD.

幽门螺杆菌（Hp）感染与胃肠外系统疾病的关系备受关注，其作为冠心病（CHD）危险因素之一，已成为心血管领域研究热点。新近发现外泌体（Exosome）可携带多种信号分子参与远端组织细胞信息传递及免疫调节。我们前期研究发现，动脉粥样硬化（AS）患者Hp感染组外周血循环中高表达miR-25；且Hp感染胃上皮细胞高表达miR-25，经Exosome参与内皮细胞炎症损伤；预测发现抗AS相关转录因子KLF2/4为miR-25潜在靶基因。故推测Hp感染通过Exosomal miR-25靶向抑制KLF2/4介导内皮细胞炎症损伤，加速AS发生发展，参与CHD致病。因此，本研究拟通过干预miR-25表达，明确Hp感染相关Exosome对内皮细胞损伤影响；确定miR-25靶基因及调控机制；并在体内验证上述效应及临床意义。预期成果将为明确Hp感染导致内皮细胞炎症损伤提供新的线索，对优化CHD防治策略提供新的思路。

幽门螺杆菌（Hp）感染与胃肠外系统疾病的关系备受关注，其作为冠心病（CHD）危险因素之一，已成为心血管领域研究热点。新近发现外泌体（Exosome）可携带多种信号分子参与远端组织细胞信息传递及免疫调节。我们研究发现，动脉粥样硬化（AS）患者Hp感染组外周血循环中高表达miR-25；且Hp感染胃上皮细胞高表达miR-25，经过表达或抑制miR-25表达，发现经Exosomal miR-25参与内皮细胞炎症损伤；生物信息学预测发现抗AS相关转录因子KLF2/4为miR-25潜在靶基因，经siRNA技术沉默靶基因表达后，发现Hp感染通过Exosomal miR-25靶向抑制KLF2/4,通过调控NF-κB信号通路，从而引起IL-6, MCP-1, VACM-1 and ICAM-1相关炎症因子表达上调，进而介导内皮细胞炎症损伤，加速AS发生发展，参与CHD致病。因此，本研究拟通过干预miR-25表达，明确Hp感染相关Exosome对内皮细胞损伤影响；确定miR-25靶基因及调控机制；并在体内验证上述效应及临床意义。预期成果将为明确Hp感染导致内皮细胞炎症损伤提供新的线索，对优化CHD防治策略提供新的思路。