血管并发症是糖尿病患者高发病率和高死亡率的主要原因。糖尿病患者在血糖得到控制后，慢性炎症和血管病变持续进展，提示存在高血糖"代谢记忆"。但高血糖"代谢记忆"分子机制远未阐明。BAG3是共分子伴侣BAG家族一员，发挥许多生物学功能。最新研究表明BAG3在心脏疾病中发挥重要功能。除心肌和骨骼肌外，正常组织很少表达BAG3，但在许多应激情况下，BAG3可被诱导表达。我们前期研究首次发现随传代次数增加，原代大鼠血管平滑肌细胞开始表达BAG3。高糖增加BAG3的表达并促进其向核内的转运，并且在短暂高糖处理恢复常糖培养后，该效果持续存在。另外，我们发现BAG3的表达水平与炎性因子表达正相关。这些结果提示BAG3表达增加及其核内定位可能与血管平滑肌细胞的高糖"代谢记忆"有关。本项目拟阐明BAG3在糖尿病血管平滑肌细胞高糖"代谢记忆"中的作用及其可能机制，可能为糖尿病血管病变的治疗带来全新的思路和方法。

Vascular complications are the main cause of diabetic patients with high morbidity and high mortality. It is evident that metabolic memory, whereby diabetic vascular complications continue to develop and progress in individuals who returned to normal glycemic control after a period of transient hyperglycemia, has long lasting effects. The mechanisms underlying metabolic memory remain largely unclarified. BAG3 is a member of BAG family with multiple cellular functions. Recent studies imply an important role of BAG3 in cardiac diseasese.Normal tissues seldom express BAG3, except for cardiomyocyte and skeletal muscle cells, but many stressful stimuli induce its expression. For the first time, we found that BAG3 expression was increased with continued passages in cultured primary rat vascular smooth muscle cells (VSMCs). We also demonstrated that high glucose increased BAG3 expression and promoted its nuclear translocation. Importantly, transient exposure to high glucose resulted in lasted increase in BAG3 expression and nuclear localization. We also demonstrated that BAG3 positively regulated the expression of inflammatory factors. Collectively, our previous data indicated that increase in BAG3 expression and its nuclear localization may play a potential role in metabolic memory of VSMCs. The current project aims to clarify the role of BAG3 in metabolic memory of diabetic vascular complications, as well as the underlying mechanisms. This project may enhance our understanding on metabolic memory of diabetic vascular complications, and may provide a potential target for combating with diabetic vascular complications.