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Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension
Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2-[18F]fluoro-2-deoxy-D-g...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649443/ https://www.ncbi.nlm.nih.gov/pubmed/34888034 http://dx.doi.org/10.1177/20458940211054325 |
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author | Farha, Samar Comhair, Suzy Hou, Yuan Park, Margaret M. Sharp, Jacqueline Peterson, Laura Willard, Belinda Zhang, Renliang DiFilippo, Frank P. Neumann, Donald Tang, W.H. Wilson Cheng, Feixiong Erzurum, Serpil |
author_facet | Farha, Samar Comhair, Suzy Hou, Yuan Park, Margaret M. Sharp, Jacqueline Peterson, Laura Willard, Belinda Zhang, Renliang DiFilippo, Frank P. Neumann, Donald Tang, W.H. Wilson Cheng, Feixiong Erzurum, Serpil |
author_sort | Farha, Samar |
collection | PubMed |
description | Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography, we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RV systolic pressure (p < 0.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p < 0.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at five years follow-up, log-ranked p = 0.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine-nitric oxide metabolism, tricarboxylic acid cycle, and ketones metabolism. Integrative human protein-protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, tricarboxylic acid cycle, purine metabolism, hypoxia-inducible factor 1, and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes. |
format | Online Article Text |
id | pubmed-8649443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-86494432021-12-08 Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension Farha, Samar Comhair, Suzy Hou, Yuan Park, Margaret M. Sharp, Jacqueline Peterson, Laura Willard, Belinda Zhang, Renliang DiFilippo, Frank P. Neumann, Donald Tang, W.H. Wilson Cheng, Feixiong Erzurum, Serpil Pulm Circ Original Research Article Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography, we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RV systolic pressure (p < 0.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p < 0.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at five years follow-up, log-ranked p = 0.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine-nitric oxide metabolism, tricarboxylic acid cycle, and ketones metabolism. Integrative human protein-protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, tricarboxylic acid cycle, purine metabolism, hypoxia-inducible factor 1, and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes. SAGE Publications 2021-11-25 /pmc/articles/PMC8649443/ /pubmed/34888034 http://dx.doi.org/10.1177/20458940211054325 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Article Farha, Samar Comhair, Suzy Hou, Yuan Park, Margaret M. Sharp, Jacqueline Peterson, Laura Willard, Belinda Zhang, Renliang DiFilippo, Frank P. Neumann, Donald Tang, W.H. Wilson Cheng, Feixiong Erzurum, Serpil Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension |
title | Metabolic endophenotype associated with right ventricular glucose
uptake in pulmonary hypertension |
title_full | Metabolic endophenotype associated with right ventricular glucose
uptake in pulmonary hypertension |
title_fullStr | Metabolic endophenotype associated with right ventricular glucose
uptake in pulmonary hypertension |
title_full_unstemmed | Metabolic endophenotype associated with right ventricular glucose
uptake in pulmonary hypertension |
title_short | Metabolic endophenotype associated with right ventricular glucose
uptake in pulmonary hypertension |
title_sort | metabolic endophenotype associated with right ventricular glucose
uptake in pulmonary hypertension |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649443/ https://www.ncbi.nlm.nih.gov/pubmed/34888034 http://dx.doi.org/10.1177/20458940211054325 |
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