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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)...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9294162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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