Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Faculty of Medicine, School of Medicine, Fu Jen Catholic University, Taipei City, Taiwan.
Am J Chin Med. 2020;48(2):341-356. doi: 10.1142/S0192415X20500172. Epub 2020 Mar 5.
MicroRNA 145 (miR-145) is a critical modulator of cardiovascular diseases. The downregulation of myocardial miR-145 is followed by an increase in disabled-2 (Dab2) expression in cardiomyocytes. (-)-epigallocatechin gallate (EGCG) is a flavonoid that has been evaluated extensively due to its diverse pharmacological properties including anti-inflammatory effects. The aim of this study was to investigate the cardioprotective effects of EGCG under hypoxia-induced stress and . The hypoxic insult led to the suppression of miR-145 expression in cultured rat cardiomyocytes in a concentration-dependent manner. Western blotting and real-time PCR were performed. In rat myocardial infarction study, hybridization, and immunofluorescent analyses were adopted. The western blot and real-time PCR data revealed that hypoxic stress with 2.5% O suppressed the expression of miR-145 and Wnt3a/-catenin in cultured rat cardiomyocytes but augmented Dab2. Treatment with EGCG attenuated Dab2 expression, but increased Wnt3a and -catenin in hypoxic cultured cardiomyocytes. Following myocardial infarction (MI) study, the data revealed the myocardial infarct area reduced by 48.5%, 44.6%, and 48.5% in EGCG (50mg/kg) or miR-145 dominant or Dab2 siRNA groups after myocardial infarction for 28 days, respectively. This study demonstrated that EGCG increased miR-145, Wnt3a, and -catenin expression but attenuated Dab2 expression. Moreover, EGCG ameliorated myocardial ischemia . The novel suppressive effect was mediated through the miR-145 and Dab2/Wnt3a/-catenin pathways.
miR-145（miR-145）是心血管疾病的关键调节因子。心肌 miR-145 的下调会导致心肌细胞中Disabled-2（Dab2）表达增加。（-）-表没食子儿茶素没食子酸酯（EGCG）是一种类黄酮，由于其具有多种药理学特性，包括抗炎作用，因此已被广泛评估。本研究旨在探讨 EGCG 在缺氧应激下的心脏保护作用。缺氧刺激以浓度依赖性方式抑制培养的大鼠心肌细胞中 miR-145 的表达。进行了 Western blot 和实时 PCR。在大鼠心肌梗死研究中，采用杂交和免疫荧光分析。Western blot 和实时 PCR 数据显示，2.5% O 的低氧应激抑制了培养的大鼠心肌细胞中 miR-145 和 Wnt3a/-catenin 的表达，但增加了 Dab2。EGCG 处理可减弱低氧培养心肌细胞中的 Dab2 表达，但增加 Wnt3a 和 -catenin。在心肌梗死后（MI）研究中，数据显示 EGCG（50mg/kg）或 miR-145 显性或 Dab2 siRNA 组在心肌梗死后 28 天分别使心肌梗死面积减少 48.5%、44.6%和 48.5%。这项研究表明，EGCG 增加了 miR-145、Wnt3a 和 -catenin 的表达，但减弱了 Dab2 的表达。此外，EGCG 改善了心肌缺血。这种新的抑制作用是通过 miR-145 和 Dab2/Wnt3a/-catenin 通路介导的。
