Metabolic Reprogramming in the Heart and Lung in a Murine Model of Pulmonary Arterial Hypertension

Frontiers in Cardiovascular Medicine
Jose L Izquierdo-GarciaJesus Ruiz-Cabello

Abstract

A significant glycolytic shift in the cells of the pulmonary vasculature and right ventricle during pulmonary arterial hypertension (PAH) has been recently described. Due to the late complications and devastating course of any variant of this disease, there is a great need for animal models that reproduce potential metabolic reprograming of PAH. Our objective is to study, in situ, the metabolic reprogramming in the lung and the right ventricle of a mouse model of PAH by metabolomic profiling and molecular imaging. PAH was induced by chronic hypoxia exposure plus treatment with SU5416, a vascular endothelial growth factor receptor inhibitor. Lung and right ventricle samples were analyzed by magnetic resonance spectroscopy. In vivo energy metabolism was studied by positron emission tomography. Our results show that metabolomic profiling of lung samples clearly identifies significant alterations in glycolytic pathways. We also confirmed an upregulation of glutamine metabolism and alterations in lipid metabolism. Furthermore, we identified alterations in glycine and choline metabolism in lung tissues. Metabolic reprograming was also confirmed in right ventricle samples. Lactate and alanine, endpoints of glycolytic oxidation, were f...Continue Reading

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Citations

Dec 19, 2019·International Journal of Molecular Sciences·Jarrod W BarnesRaed A Dweik
Jun 7, 2019·Antioxidants & Redox Signaling·Olga RafikovaRuslan Rafikov
Jun 23, 2020·Oxidative Medicine and Cellular Longevity·Damian GajeckiAdrian Doroszko
May 8, 2020·International Journal of Molecular Sciences·Susana Carregal-RomeroJesús Ruíz-Cabello
Mar 6, 2019·Cells·Ilias MylonisEfrosyni Paraskeva
Sep 3, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chao YuanGuo-Wei He
Feb 11, 2021·Annual Review of Physiology·Weiling XuSerpil C Erzurum
Aug 12, 2021·Expert Reviews in Molecular Medicine·Sachendra Pratap SinghAshish Gupta

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Methods Mentioned

BETA
nuclear magnetic resonance
metabolomic profiling
NMR
PCA

Software Mentioned

MestRenova
Metabonomic
G Power
NIS
Elements

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