Liao Rongheng, Qi Zhen, Tang Ri, Wang Renrong, Wang Yongyi
Department of Cardiovascular Surgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Critical Care Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Front Pharmacol. 2021 Aug 17;12:714390. doi: 10.3389/fphar.2021.714390. eCollection 2021.
Myocardial fibrosis is a key pathological process after myocardial infarction, which leads to poor outcomes in patients at the end stage. Effective treatments for improving prognosis of myocardial fibrosis are needed to be further developed. Methyl ferulic acid (MFA), a biologically active monomer extracted and purified from the Chinese herbal medicine, is reported as an attenuator in many diseases. In this study, we aim to reveal the role it plays in myocardial fibrosis after myocardial infarction and its possible mechanism. Firstly, we found that MFA attenuated the expression of fibrosis-related proteins and the ability of migration and proliferation in TGF-β1-induced human cardiac fibroblasts (HCFs). Then, myocardial fibrosis after myocardial infarction models on mouse was built to reveal the affection of MFA. After 28 days of treatments, fibrosis areas, cardiac function, and expression of fibrosis-related proteins were all improved in the MFA-treated group than the myocardial infarction group. Finally, to elucidate the mechanism of phenomenon we observed, we found that MFA attenuated HCF differentiation after myocardial infarction by suppressing the migration and proliferation in HCFs, which was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway. Our findings showed that MFA attenuated the expression of fibrosis-related proteins, and the ability of migration and proliferation in HCFs improved the cardiac function of myocardial infarction mice; meanwhile, the mechanism of that was by suppressing the pRB-E2F1/CCNE2 and the RhoA/ROCK2 pathway.
心肌纤维化是心肌梗死后的关键病理过程，会导致终末期患者预后不良。需要进一步开发有效治疗方法来改善心肌纤维化的预后。阿魏酸甲酯（MFA）是从中药中提取纯化的生物活性单体，在许多疾病中被报道为一种减毒剂。在本研究中，我们旨在揭示其在心肌梗死后心肌纤维化中所起的作用及其可能机制。首先，我们发现MFA可减弱转化生长因子-β1（TGF-β1）诱导的人心脏成纤维细胞（HCFs）中纤维化相关蛋白的表达以及迁移和增殖能力。然后，构建小鼠心肌梗死后心肌纤维化模型以揭示MFA的影响。治疗28天后，MFA治疗组的纤维化面积、心脏功能及纤维化相关蛋白的表达均比心肌梗死组有所改善。最后，为阐明我们观察到的现象的机制，我们发现MFA通过抑制HCFs的迁移和增殖来减弱心肌梗死后HCF的分化，这是通过抑制pRB-E2F1/CCNE2和RhoA/ROCK2途径实现的。我们的研究结果表明，MFA减弱了纤维化相关蛋白的表达，改善了HCFs的迁移和增殖能力，进而改善了心肌梗死小鼠的心脏功能；同时，其机制是通过抑制pRB-E2F1/CCNE2和RhoA/ROCK2途径。
