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Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension

Right ventricular failure (RVF) is the independent and strongest predictor of mortality in pulmonary arterial hypertension (PAH), but, at present, there are no preventive and therapeutic strategies directly targeting the failing right ventricle (RV). The underlying mechanism of RV hypertrophy (RVH)...

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Autores principales: Qin, Xiaohan, Lei, Chuxiang, Yan, Li, Sun, Haidan, Liu, Xiaoyan, Guo, Zhengguang, Sun, Wei, Guo, Xiaoxiao, Fang, Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294162/
https://www.ncbi.nlm.nih.gov/pubmed/35865003
http://dx.doi.org/10.3389/fmolb.2022.834179
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author Qin, Xiaohan
Lei, Chuxiang
Yan, Li
Sun, Haidan
Liu, Xiaoyan
Guo, Zhengguang
Sun, Wei
Guo, Xiaoxiao
Fang, Quan
author_facet Qin, Xiaohan
Lei, Chuxiang
Yan, Li
Sun, Haidan
Liu, Xiaoyan
Guo, Zhengguang
Sun, Wei
Guo, Xiaoxiao
Fang, Quan
author_sort Qin, Xiaohan
collection PubMed
description Right ventricular failure (RVF) is the independent and strongest predictor of mortality in pulmonary arterial hypertension (PAH), but, at present, there are no preventive and therapeutic strategies directly targeting the failing right ventricle (RV). The underlying mechanism of RV hypertrophy (RVH) and dysfunction needs to be explored in depth. In this study, we used myocardial proteomics combined with metabolomics to elucidate potential pathophysiological changes of RV remodeling in a monocrotaline (MCT)-induced PAH rat model. The proteins and metabolites extracted from the RV myocardium were identified using label-free liquid chromatography–tandem mass spectrometry (LC-MS/MS). The bioinformatic analysis indicated that elevated intracellular Ca(2+) concentrations and inflammation may contribute to myocardial proliferation and contraction, which may be beneficial for maintaining the compensated state of the RV. In the RVF stage, ferroptosis, mitochondrial metabolic shift, and insulin resistance are significantly involved. Dysregulated iron homeostasis, glutathione metabolism, and lipid peroxidation related to ferroptosis may contribute to RV decompensation. In conclusion, we depicted a proteomic and metabolomic profile of the RV myocardium during the progression of MCT-induced PAH, and also provided the insights for potential therapeutic targets facilitating the retardation or reversal of RV dysfunction in PAH.
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spelling pubmed-92941622022-07-20 Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension Qin, Xiaohan Lei, Chuxiang Yan, Li Sun, Haidan Liu, Xiaoyan Guo, Zhengguang Sun, Wei Guo, Xiaoxiao Fang, Quan Front Mol Biosci Molecular Biosciences Right ventricular failure (RVF) is the independent and strongest predictor of mortality in pulmonary arterial hypertension (PAH), but, at present, there are no preventive and therapeutic strategies directly targeting the failing right ventricle (RV). The underlying mechanism of RV hypertrophy (RVH) and dysfunction needs to be explored in depth. In this study, we used myocardial proteomics combined with metabolomics to elucidate potential pathophysiological changes of RV remodeling in a monocrotaline (MCT)-induced PAH rat model. The proteins and metabolites extracted from the RV myocardium were identified using label-free liquid chromatography–tandem mass spectrometry (LC-MS/MS). The bioinformatic analysis indicated that elevated intracellular Ca(2+) concentrations and inflammation may contribute to myocardial proliferation and contraction, which may be beneficial for maintaining the compensated state of the RV. In the RVF stage, ferroptosis, mitochondrial metabolic shift, and insulin resistance are significantly involved. Dysregulated iron homeostasis, glutathione metabolism, and lipid peroxidation related to ferroptosis may contribute to RV decompensation. In conclusion, we depicted a proteomic and metabolomic profile of the RV myocardium during the progression of MCT-induced PAH, and also provided the insights for potential therapeutic targets facilitating the retardation or reversal of RV dysfunction in PAH. Frontiers Media S.A. 2022-07-05 /pmc/articles/PMC9294162/ /pubmed/35865003 http://dx.doi.org/10.3389/fmolb.2022.834179 Text en Copyright © 2022 Qin, Lei, Yan, Sun, Liu, Guo, Sun, Guo and Fang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Qin, Xiaohan
Lei, Chuxiang
Yan, Li
Sun, Haidan
Liu, Xiaoyan
Guo, Zhengguang
Sun, Wei
Guo, Xiaoxiao
Fang, Quan
Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension
title Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension
title_full Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension
title_fullStr Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension
title_full_unstemmed Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension
title_short Proteomic and Metabolomic Analyses of Right Ventricular Failure due to Pulmonary Arterial Hypertension
title_sort proteomic and metabolomic analyses of right ventricular failure due to pulmonary arterial hypertension
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294162/
https://www.ncbi.nlm.nih.gov/pubmed/35865003
http://dx.doi.org/10.3389/fmolb.2022.834179
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