心肌梗死(MI),一种高死亡率的普遍心脏疾病,导致与炎症和心肌细胞凋亡相关的严重心脏损伤。已广泛发现长链非编码RNA参与MI的进展。这里,我们旨在探讨lincRNA-红细胞前存活(EPS)对MI诱导的炎症和心肌细胞凋亡的影响.重要的是,lincRNA-EPS在MI小鼠和氧和葡萄糖剥夺(OGD)处理的HL-1细胞中表达低。超声心动图分析显示lincRNA-EPS过表达增加左心室射血分数和左心室缩短率,在小鼠模型中,收缩末期左心室内径和舒张末期左心室内径减小。在我们的研究中,白细胞介素-6、肿瘤坏死因子-α、白细胞介素-1β,和白细胞介素-18在MI小鼠和OGD处理的HL-1细胞中上调,而lincRNA-EPS过表达逆转了这些表型。同时,lincRNA-EPS在体内和体外减少MI诱导的心肌细胞凋亡。机械上,lincRNA-EPS与肌球蛋白重链6(MYH6)和异质核核糖核蛋白L(HNRNPL)相互作用,lincRNA-EPS和HNRNPL的消耗抑制了HL-1细胞中MYH6mRNA的稳定性。HNRNPL敲低阻断lincRNA-EPS过表达诱导的系统中MYH6表达。MYH6和HNRNPL的消耗可以挽救HL-1细胞中lincRNA-EPS过表达减少的炎症和凋亡。因此,我们得出的结论是,lincRNA-EPS通过募集HNRNPL维持MYH6稳定性,从而减轻MI诱导的心肌损伤中的炎症和凋亡。
Myocardial infarction (MI), a prevalent cardiac disorder with high mortality, leads to severe heart injury associated with inflammation and cardiomyocyte apoptosis. Long non-coding RNAs have been widely found to participate in the progression of MI. Here, we aimed to explore the impact of lincRNA-erythroid prosurvival (EPS) on MI-induced inflammation and cardiomyocyte apoptosis. Significantly, lincRNA-EPS was lowly expressed in MI mice and in oxygen and glucose deprivation (OGD)-treated HL-1 cells. Echocardiography analysis revealed that lincRNA-EPS overexpression increased left ventricular ejection fraction and left ventricular fraction shortening, and decreased left ventricular internal diameter at end systole and left ventricular internal diameter at end diastole in a mouse model. In our study, the expression levels of interleukin-6, tumor necrosis factor-alpha, interleukin-1β, and interleukin-18 were upregulated in the MI mice and OGD-treated HL-1 cells, while lincRNA-EPS overexpression reversed these phenotypes. Meanwhile, lincRNA-EPS reduced MI-induced cardiomyocyte apoptosis in vivo and in vitro. Mechanically, lincRNA-EPS interacted with myosin heavy chain 6 (
MYH6) and heterogeneous nuclear ribonucleoprotein L (HNRNPL), and the depletion of lincRNA-EPS and HNRNPL inhibited
MYH6 mRNA stability in HL-1 cells. HNRNPL knockdown blocked lincRNA-EPS overexpression-induced
MYH6 expression in the system. The depletion of
MYH6 and HNRNPL could rescue lincRNA-EPS overexpression-reduced inflammation and apoptosis in HL-1 cells. Thus, we conclude that lincRNA-EPS attenuates inflammation and apoptosis in MI-induced myocardial injury by maintaining
MYH6 stability through the recruitment of HNRNPL.