心梗后心肌/内皮细胞产生不同形式CTRP9（球状片段/全长蛋白）调控心肌间质纤维化机制研究

心梗后启动以心肌间质纤维化为典型表现的病理性心肌重构，是导致病人心衰、死亡重要原因，但心肌调控间质纤维化机制仍不清楚。我们在Circulation报道了外源性CTRP9球状片段（gCTRP9）可显著抑制心梗后间质纤维化，阻遏病理性心肌重构。其它研究组报道全长CTRP9（fCTRP9）会增加Tac模型心肌肥厚及间质纤维化，提示不同形式或来源CTRP9对于心肌间质纤维化作用及机制不同。我们预试验结果发现心肌细胞主要产生gCTRP9，内皮细胞主要产生fCTRP9，心肌细胞-成纤维细胞共培养示gCTRP9可通过心肌细胞抑制成纤维细胞增殖，而fCTRP9促进成纤维细胞增殖。因此提出科学假说：心梗后心肌/内皮细胞产生不同形式CTRP9（球状片段/全长蛋白），通过维系其平衡，调控细胞间通讯关键分子PEDF，干预心肌间质纤维化进程。有望为心梗后病理性心肌重构提供新的干预靶点,具有重要的理论价值与应用前景。

Myocardial fibrosis as a typical manifestation of pathological myocardial remodeling after myocardial infarction, leads to long-term death of patients. However, the specific mechanism of myocardial interstitial fibrosis after myocardial infarction remains unclear. We first reported in Circulation that globular CTRP9 significantly inhibited myocardial interstitial fibrosis after myocardial infarction. While full-length CTRP9 increased cardiac hypertrophy and interstitial fibrosis in Tac model, suggesting that different sources or different forms of CTRP9 may play different roles in myocardial interstitial fibrosis. Our preliminary data showed that cardiomyocytes mainly produce gCTRP9, and endothelial cells mainly produce fCTRP9. Cardiomyocyte-fibroblast co-culture experiment shows that gCTRP9 can inhibit proliferation of fibroblasts while fCTRP9 promotes proliferation of fibroblasts. Therefore, we propose the following scientific hypothesis: Cardiomyocytes/ endothelial cells produce different forms of CTRP9 (gCTRP9/fCTRP9) after myocardial infarction, interfering with the process of myocardial interstitial fibrosis by maintaining its balance and regulating PEDF, a key intercellular communication molecule. It is expected to provide a new target for myocardial remodeling, which has important theoretical value and application prospects.