Abstract：
Myocardial fibrosis is a pathological, physiological change that results from alterations, such as inflammation and metabolic dysfunction, after myocardial infarction (MI). Excessive fibrosis can cause cardiac dysfunction, ventricular remodeling, and heart failure. Caffeic acid (CA), a natural polyphenolic acid in various foods, has cardioprotective effects. This study aimed to explore whether CA exerts a cardioprotective effect to inhibit myocardial fibrosis post-MI and elucidate the underlying mechanisms. Histological observations indicated that CA ameliorated ventricular remodeling induced by left anterior descending coronary artery ligation in MI mice and partially restored cardiac function. CA selectively targeted transforming growth factor-β receptor 1 (TGFBR1) and inhibited TGFBR1-Smad2/3 signaling, reducing collagen deposition in the infarcted area of MI mice hearts. Furthermore, cell counting (CCK-8) assay, 5-ethynyl-2\'-deoxyuridine assay, and western blotting revealed that CA dose-dependently decreased the proliferation, collagen synthesis, and activation of the TGFBR1-Smad2/3 pathway in primary cardiac fibroblasts (CFs) stimulated by TGF-β1 in vitro. Notably, TGFBR1 overexpression in CFs partially counteracted the inhibitory effects of CA. These findings suggest that CA effectively mitigates myocardial fibrosis and enhances cardiac function following MI and that this effect may be associated with the direct targeting of TGFBR1 by CA.
摘要：
心肌纤维化是一种病理性,由变化引起的生理变化，如炎症和代谢功能障碍，心肌梗死（MI）后。过度的纤维化会导致心脏功能障碍,心室重构,和心力衰竭。咖啡酸(CA),各种食品中的天然多酚酸，有心脏保护作用.本研究旨在探讨CA是否具有心肌保护作用以抑制MI后心肌纤维化，并阐明其潜在机制。组织学观察表明，CA改善了MI小鼠左冠状动脉前降支结扎引起的心室重构，并部分恢复了心功能。CA选择性靶向转化生长因子-β受体1（TGFBR1）并抑制TGFBR1-Smad2/3信号传导，减少心肌梗死小鼠心脏梗死区的胶原沉积。此外，细胞计数（CCK-8）测定，5-乙炔基-2'-脱氧尿苷测定，和蛋白质印迹显示CA剂量依赖性地减少增殖，胶原蛋白合成，和体外TGF-β1刺激的原代心脏成纤维细胞（CFs）中TGFBR1-Smad2/3途径的激活。值得注意的是,CFs中的TGFBR1过表达部分抵消了CA的抑制作用。这些发现表明CA有效地减轻心肌纤维化并增强MI后的心脏功能，并且这种作用可能与CA直接靶向TGFBR1有关。
