急性心肌梗死（AMI）是首位心血管死亡原因。蛋白多糖4（PRG4）由富含生物活性的粘多糖及核心蛋白构成，最新研究发现PRG4参与炎症反应并可抑制软骨细胞凋亡，且可通过Toll样受体2/4（TLR2/4）抑制炎症因子，但其在心脏疾病中的作用尚无研究。Toll样受体在心肌细胞及炎症细胞上广泛表达,TLR2/4缺失可改善AMI心肌细胞凋亡及心脏重构。我们预实验研究发现AMI急性期PRG4表达增多；体外实验表明PRG4主要由心肌细胞表达，且心肌细胞缺氧凋亡时，PRG4被分泌至细胞外。因此我们推测心肌细胞分泌的PRG4可能通过TLR2/4通路调控心肌细胞细胞凋亡在AMI中发挥作用。本项目拟采用PRG4基因敲除及过表达小鼠AMI模型，基因过表达及干扰等技术，阐明PRG4在AMI中调控心肌细胞凋亡的机制。本研究有助于阐明AMI发病机制和寻找潜在药物作用靶点。

Acute myocardial infarction(AMI) is the leading cause of cardiovascular death. Proteoglycan 4 (PRG4) is composed of a core protein with covalently attached glycosaminoglycans (GAGs), which could interact with growth factors, cytokines and growth factor receptors. Latest studies revealed a significant role of PRG4 in suppressing inflammation by interacting with Toll-like receptor 2/4 (TLR2/4). Besides, PRG4 is also involved in chondrocyte apoptosis. Nevertheless, PRG4 has never been investigated in AMI. Toll-like receptors are expressed on cardiomyocytes. Loss of TLR2/4 is associated with reduced expression of inflammatory cytokines and improvement of cardiac remodeling. Our preliminary study showed that PRG4 is upregulated in the acute phase of AMI. In vitro study demonstrated that PRG4 is mainly expressed in cardiomyocytes, and excreted into extracellular space during cardiomyocyte apoptosis. Hence, we hypothesized that PRG4 affects the progression of AMI via regulating cardiomyocyte apoptosis through TLR2/4 pathway. Therefore, we will employ PRG4 knockout and overexpressing mouse AMI models, gene overexpression and knockdown technology to verify whether PRG4 affects the progression of AMI via TLR2/4. Our study is expected to disclose new mechanisms of pathogenesis of AMI and to provide evidence for PRG4 as a new therapy target for clinics.