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l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation
Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that de...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326551/ https://www.ncbi.nlm.nih.gov/pubmed/35911183 http://dx.doi.org/10.1002/pul2.12107 |
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author | Agrawal, Vineet Hemnes, Anna R. Shelburne, Nicholas J. Fortune, Niki Fuentes, Julio L. Colvin, Dan Calcutt, Marion W. Talati, Megha Poovey, Emily West, James D. Brittain, Evan L. |
author_facet | Agrawal, Vineet Hemnes, Anna R. Shelburne, Nicholas J. Fortune, Niki Fuentes, Julio L. Colvin, Dan Calcutt, Marion W. Talati, Megha Poovey, Emily West, James D. Brittain, Evan L. |
author_sort | Agrawal, Vineet |
collection | PubMed |
description | Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l‐carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation. In vivo in transgenic mice harboring a human BMPR2 mutation, l‐carnitine supplementation reversed RV failure by increasing RV cardiac output, improving RV ejection fraction, and decreasing RV lipid accumulation through increased PPARγ expression and augmented fatty acid oxidation of long chain fatty acids. These findings were confirmed in a second model of pulmonary artery banding‐induced RV dysfunction. In vitro, l‐carnitine supplementation selectively increased fatty acid oxidation in mitochondria and decreased lipid accumulation through a Cpt1‐dependent pathway. l‐Carnitine supplementation improves right ventricular contractility in the stressed RV through augmentation of fatty acid oxidation and decreases lipid accumulation. Correction of carnitine deficiency through l‐carnitine supplementation in PAH may reverse RV failure. |
format | Online Article Text |
id | pubmed-9326551 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93265512022-07-30 l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation Agrawal, Vineet Hemnes, Anna R. Shelburne, Nicholas J. Fortune, Niki Fuentes, Julio L. Colvin, Dan Calcutt, Marion W. Talati, Megha Poovey, Emily West, James D. Brittain, Evan L. Pulm Circ Research Articles Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l‐carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation. In vivo in transgenic mice harboring a human BMPR2 mutation, l‐carnitine supplementation reversed RV failure by increasing RV cardiac output, improving RV ejection fraction, and decreasing RV lipid accumulation through increased PPARγ expression and augmented fatty acid oxidation of long chain fatty acids. These findings were confirmed in a second model of pulmonary artery banding‐induced RV dysfunction. In vitro, l‐carnitine supplementation selectively increased fatty acid oxidation in mitochondria and decreased lipid accumulation through a Cpt1‐dependent pathway. l‐Carnitine supplementation improves right ventricular contractility in the stressed RV through augmentation of fatty acid oxidation and decreases lipid accumulation. Correction of carnitine deficiency through l‐carnitine supplementation in PAH may reverse RV failure. John Wiley and Sons Inc. 2022-07-01 /pmc/articles/PMC9326551/ /pubmed/35911183 http://dx.doi.org/10.1002/pul2.12107 Text en © 2022 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Agrawal, Vineet Hemnes, Anna R. Shelburne, Nicholas J. Fortune, Niki Fuentes, Julio L. Colvin, Dan Calcutt, Marion W. Talati, Megha Poovey, Emily West, James D. Brittain, Evan L. l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation |
title |
l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation |
title_full |
l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation |
title_fullStr |
l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation |
title_full_unstemmed |
l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation |
title_short |
l‐Carnitine therapy improves right heart dysfunction through Cpt1‐dependent fatty acid oxidation |
title_sort | l‐carnitine therapy improves right heart dysfunction through cpt1‐dependent fatty acid oxidation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326551/ https://www.ncbi.nlm.nih.gov/pubmed/35911183 http://dx.doi.org/10.1002/pul2.12107 |
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