SMOC-1作为BMP内源性抑制物参与心肌梗死后心脏破裂发生的作用及机制研究

细胞外基质（ECM）非结构分子在心梗后心脏破裂中起关键作用。我们前期通过蛋白质组学及扩大样本验证发现，分泌性模块化钙结合白-1（SMOC-1）在破裂患者血浆中高表达。研究证实，SMOC-1作为ECM非结构分子在低等生物中抑制骨形态发生蛋白（BMP）信号。BMP信号又是梗死后ECM损伤和修复的重要通路。我们假设：SMOC-1通过抑制BMP信号参与心脏破裂。本项目拟利用SMOC-1心肌特异性敲除小鼠和重组腺相关病毒介导SMOC-1高表达的小鼠建立心梗模型，研究SMOC-1与心脏破裂的关系。紧接着，基于上述模型探索SMOC-1对梗死后ECM损伤和修复的影响。随后，利用BMP抑制剂干预SMOC-1心肌特异性敲除小鼠心梗模型，证实SMOC-1通过BMP参与心脏破裂的机制。最后，细胞实验明确SMOC-1参与心脏破裂的机制。本项目将阐明SMOC-1参与心脏破裂的全新机制，为心脏破裂的防治提供新靶点。

Extracellular matrix (ECM) non-structural molecules play a key role in cardiac rupture (CR) after myocardial infarction (MI). Previously, we found that secreted modular calcium-binding protein 1 (SMOC-1) was highly expressed in ruptured patients' plasma by proteomics and enlarged sample validation. Studies have confirmed that SMOC-1, as a non-structural molecule of ECM, inhibits bone morphogenetic protein (BMP) signaling in lower organisms. BMP signaling is an important pathway for ECM injury and repair after infarction. Thus, we hypothesize that SMOC-1 participates in CR by inhibiting BMP signaling. This project intends to establish a MI model using SMOC-1 myocardial-specific knockout (SMOC-1-/-) mice and recombinant adeno-associated virus-mediated SMOC-1 high expression mice to study the relationship between SMOC-1 and CR. Next, we will explore the effects of SMOC-1 on post-infarction ECM injury and repair. Subsequently, BMP inhibitors were used to intervene in the MI model of SMOC-1-/- mice, confirming the mechanism by which SMOC-1 participates in CR through BMP. Finally, cell experiments identified the mechanism of SMOC-1 involvement in CR. This project will clarify the new mechanism of SMOC-1 participating in CR, and provide new strategies and targets for CR therapy.