2026-06-14T03:33:13Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/72342024-09-27T09:18:41Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Izquierdo-Garcia, Jose L.
author
Arias, Teresa
author
Rojas, Yeny
author
Garcia-Ruiz, Victoria
author
Santos, Arnoldo
author
Martin-Puig, Silvia
author
Ruiz-Cabello, Jesus
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Comisión Europea
funder
Fundación ProCNIC
2019-02-25T13:36:03Z
2019-02-25T13:36:03Z
2018
Front Cardiovasc Med. 2018; 5:110
10.3389/fcvm.2018.00110
2297-055X
Frontiers in cardiovascular medicine
30159317
http://hdl.handle.net/20.500.12105/7234
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 found to have increased concentrations in mice with PAH. Glutamine and taurine concentrations were correlated to specific ventricle hypertrophy features. We demonstrated that most of the metabolic features that characterize human PAH were detected in a hypoxia plus SU5416 mouse model and it may become a valuable tool to test new targeting treatments of this severe disease.
eng
NMR spectroscopy
Metabolomics
Molecular imaging
Preclinical models
Pulmonary arterial hypertension
Metabolic Reprogramming in the Heart and Lung in a Murine Model of Pulmonary Arterial Hypertension
journal article
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MetabolicReprogrammingInTheHeart _2018.pdf
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https://repisalud.isciii.es/bitstreams/4f5d1852-25ff-41f9-8e80-731d9986eaeb/download
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MetabolicReprogrammingInTheHeart _2018.pdf.txt