Alterations in Mitochondrial Oxidative Phosphorylation System: Relationship of Complex V and Cardiac Dysfunction in Human Heart Failure.

Autor: Giménez-Escamilla I; 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., Benedicto C; Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IIS La Fe), Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain., Pérez-Carrillo L; 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., Delgado-Arija M; 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., González-Torrent I; Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IIS La Fe), Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain., Vilchez R; Neuromuscular and Ataxias Research Group, Health Research Institute Hospital La Fe (IIS La Fe), Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Avd. Monforte de Lemos 3-5, 28029 Madrid, Spain., Martínez-Dolz L; 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.; Heart Failure and Transplantation Unit, Cardiology Department, University and Polytechnic La Fe Hospital, Avd. Fernando Abril Martorell 106, 46026 Valencia, Spain., Portolés M; 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., Tarazón E; 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., Roselló-Lletí E; 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.
Jazyk: angličtina
Zdroj: Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2024 Feb 26; Vol. 13 (3). Date of Electronic Publication: 2024 Feb 26.
DOI: 10.3390/antiox13030285
Abstrakt: 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.
Databáze: MEDLINE