Giménez-Escamilla Isaac, Benedicto Carlota, Pérez-Carrillo Lorena, Delgado-Arija Marta, González-Torrent Irene, Vilchez Roger, Martínez-Dolz Luis, Portolés Manuel, Tarazón Estefanía, Roselló-Lletí Esther
Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IIS La Fe), Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain.
Center for Biomedical Research Network on Cardiovascular Diseases (CIBERCV), Avd. Monforte de Lemos 3-5, 28029 Madrid, Spain.
Antioxidants (Basel). 2024 Feb 26;13(3):285. doi: 10.3390/antiox13030285.
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 = 36; ncRNA = 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, (ICM, FC = 2.04; < 0.01), (ICM, FC = 1.33, < 0.05), and (ICM, FC = 1.81; < 0.001), which presented a significant correlation with established echocardiographic parameters of cardiac remodeling and ventricular function as follows: left ventricular end-systolic ( < 0.01) and end-diastolic ( < 0.01) diameters, and ejection fraction ( < 0.05). We also detected an increase in ATP5IF1 protein levels (ICM, FC = 1.75; < 0.01) and alterations in the microRNA expression levels of miR-208b-3p (ICM, FC = -1.44, < 0.001), miR-483-3p (ICM, FC = 1.37, < 0.01), regulators of . 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.
心力衰竭（HF）是一种与生物能量线粒体异常相关的疾病。然而，氧化磷酸化系统（OXPHOS）中涉及的分子的整体状态尚不清楚。因此，我们通过RNA测序分析（mRNA = 36；非编码RNA = 30）对心力衰竭患者（缺血性心肌病（ICM）和扩张型心肌病（DCM））及对照受试者的人心脏组织的OXPHOS转录组进行了分析。我们在这些患者中检测到28个改变的基因，突出显示ICM中存在更大程度的失调。具体而言，我们发现复合物V（ATP合酶）元件普遍过表达，其中，（ICM，FC = 2.04；<0.01），（ICM，FC = 1.33，<0.05），以及（ICM，FC = 1.81；<0.001），它们与已确立的心脏重塑和心室功能的超声心动图参数呈显著相关性，如下：左心室收缩末期（<0.01）和舒张末期（<0.01）直径，以及射血分数（<0.05）。我们还检测到ATP5IF1蛋白水平升高（ICM，FC = 1.75；<0.01）以及miR-208b-3p（ICM，FC = -1.44，<0.001）、miR-483-3p（ICM，FC = 1.37，<0.01）的微小RNA表达水平改变，它们是……的调节因子。因此，我们观察到ICM患者中OXPHOS转录组的失调，突出显示复合物V的过表达及其与心脏重塑和功能的关系。
