血管钙化普遍存在于糖尿病患者，是大血管病变的病理生理基础，是糖尿病心血管疾病发病率和死亡率均高的主要独立危险因子，但糖尿病血管钙化的发病机制尚未完全阐明。课题组前期研究证实：miR-32可促进血管钙化的发生；高糖可上调miR-32的表达并促进血管平滑肌细胞向成骨样细胞分化；GATA6及其下游信号sm-MHC/OCN/Grem1被发现可能是miR-32的作用靶点。因此，本项目提出：高糖可通过上调miR-32影响GATA6/sm-MHC/OCN/Grem1信号通路促进血管钙化的发生。项目拟在细胞水平上明确miR-32/GATA6在高糖诱导细胞钙化过程中的作用及机制；在动物模型上探讨miR-32/GATA6在糖尿病血管钙化发生发展过程中的作用及机制；在临床明确并证实miR-32/GATA6与糖尿病血管钙化发生发展的关联性及临床意义。项目的完成将为糖尿病血管钙化的防治提供新的潜在生物学靶点。

Vascular calcification commonly found in diabetic patients, is the pathophysiological basis of macrovascular disease, and is a major independent risk factor of high cardiovascular morbidity and mortality for diabetic patients. However, the pathogenesis of vascular calcification in diabetes is not yet fully understood. Our previous studies showed that miR-32 promoted vascular calcification, and it was found that high glucose could increase the expression of miR-32, rending vascular smooth muscle cells to differentiate into osteoblast-like cells. Moreover, we found that GATA6 and the downstream sm-MHC/OCN/Grem1 signaling pathways, which were closely related to vascular calcification, might be the targets of miR-32. Based on the above results, we hypothesized that high glucose could promote vascular calcification through increasing the expression of miR-32 and then regulating GATA6/sm-MHC/OCN/Grem1 signaling pathway. This project will attempt to reveal the role of miR-32/GATA6 axis in high-glucose-induced vascular calcification, and verify the clinical correlationship between miR-32/GATA6 and diabetes associated vascular calcification. The completion of this project will provide new potential biological targets for prevention and treatment of vascular calcification in diabetic patients.