Abstract:
Heart failure (HF) is a disease related to bioenergetic mitochondrial abnormalities. However, the whole status of molecules involved in the oxidative phosphorylation system (OXPHOS) is unknown. Therefore, we analyzed the OXPHOS transcriptome of human cardiac tissue by RNA-seq analyses (mRNA n = 36; ncRNA n = 30) in HF patients (ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM)) and control subjects. We detected 28 altered genes in these patients, highlighting greater deregulation in ICM. Specifically, we found a general overexpression of complex V (ATP synthase) elements, among them, ATP5I (ICM, FC = 2.04; p < 0.01), ATP5MJ (ICM, FC = 1.33, p < 0.05), and ATP5IF1 (ICM, FC = 1.81; p < 0.001), which presented a significant correlation with established echocardiographic parameters of cardiac remodeling and ventricular function as follows: left ventricular end-systolic (p < 0.01) and end-diastolic (p < 0.01) diameters, and ejection fraction (p < 0.05). We also detected an increase in ATP5IF1 protein levels (ICM, FC = 1.75; p < 0.01) and alterations in the microRNA expression levels of miR-208b-3p (ICM, FC = -1.44, p < 0.001), miR-483-3p (ICM, FC = 1.37, p < 0.01), regulators of ATP5I. Therefore, we observed the deregulation of the OXPHOS transcriptome in ICM patients, highlighting the overexpression of complex V and its relationship with cardiac remodeling and function.
摘要:
心力衰竭(HF)是与生物能线粒体异常相关的疾病。然而,参与氧化磷酸化系统(OXPHOS)的分子的整体状态是未知的。因此,我们在HF患者(缺血性心肌病(ICM)和扩张型心肌病(DCM))和对照受试者中通过RNA-seq分析(mRNAn=36;ncRNAn=30)分析了人类心脏组织的OXPHOS转录组.我们在这些患者中检测到28个改变的基因,强调ICM中更大的放松管制。具体来说,我们发现了复杂V(ATP合酶)元件的一般过度表达,其中,ATP5I(ICM,FC=2.04;p<0.01),ATP5MJ(ICM,FC=1.33,p<0.05),和ATP5IF1(ICM,FC=1.81;p<0.001),这表明与建立的心脏重塑和心室功能的超声心动图参数显着相关,如下:左心室收缩末期(p<0.01)和舒张末期(p<0.01)直径,射血分数(p<0.05)。我们还检测到ATP5IF1蛋白水平的增加(ICM,FC=1.75;p<0.01)和miR-208b-3p的microRNA表达水平的改变(ICM,FC=-1.44,p<0.001),miR-483-3p(ICM,FC=1.37,p<0.01),ATP5I的监管机构。因此,我们观察到ICM患者OXPHOS转录组的失调,强调复合物V的过度表达及其与心脏重塑和功能的关系。