AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway
AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway
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AFC1 化合物通过抑制 PDGFR 和 STAT 通路减轻 MI/R 诱导的心室重塑
DOI：
10.3389/fphar.2019.01142
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发表时间：
2019-10-15
影响因子：
5.6
通讯作者：
Liu, Zhongmin
中科院分区：
文献类型：
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作者：
Liu, Jie;Zhou, Xiaohui;Liu, Zhongmin
有效的干预措施，以改善心肌缺血/再灌注（MI/R）患者的结果是迫切的，在临床设置。丹参酮Ⅱ A（TSA）可减轻MI/R后心肌损伤，改善心室重构。在此，我们评估了与TSA结构相似的AFC 1化合物在鼠MI/R模型中的功效。我们发现AFC 1在改善MI/R后小鼠心功能方面具有相当的效果，但其安全性上级优于TSA。AFC 1的管理减少了活性氧（ROS）的产生，炎症细胞浸润，血小板衍生生长因子受体（PDGFR）在梗死心肌的表达。AFC 1治疗还减弱了MI/R诱导的心脏重构，并有助于心脏功能的恢复。此外，AFC 1在体外逆转了PDGF-AB诱导的新生大鼠心肌细胞（NCM）和新生大鼠心脏成纤维细胞（NCF）中PDGFR表达的升高，并抑制了PDGF-AB诱导的NCM肥大（通过STAT 3途径）和NCF胶原合成（通过p38-MAPK信号转导）。类似地，AFC 1可能通过抑制STAT信号传导而促进MI/R后小鼠的心脏功能恢复。我们的研究结果证实，AFC 1对MI/R诱导的心脏重构具有抗肥厚和抗纤维化作用，并表明AFC 1可能在改善MI/R患者的预后方面具有很好的潜力。
Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models. We found that AFC1 had a comparable effect of improving murine cardiac function after MI/R while it was superior to TSA in safety profile. Administration of AFC1 reduced reactive oxygen species (ROS) production, inflammatory cells infiltration, and the expression of platelet derived growth factor receptors (PDGFR) in infarcted myocardium. Treatment with AFC1 also attenuated MI/R-induced cardiac remodeling and contributed to the recovery of cardiac function. Additionally, AFC1 reversed the elevation of PDGFR expression induced by PDGF-AB in both neonatal rat cardiomyocytes (NCMs) and neonatal rat cardiac fibroblasts (NCFs) and suppressed PDGF-AB induced NCM hypertrophy via STAT3 pathway and NCF collagen synthesis through p38-MAPK signaling in vitro. Similarly, AFC1 may contribute to the recovery of cardiac function in mice post MI/R via suppressing STAT signaling. Our results confirmed that AFC1 exerts anti-hypertrophic and anti-fibrotic effects against MI/R-induced cardiac remodeling, and suggest that AFC1 may have a promising potential in improving the outcome of patients who suffered from MI/R.