Metabolomic heterogeneity of pulmonary arterial hypertension.
Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular sys...
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doaj-247447fa48864bcd8529fff7219f57432020-11-25T00:47:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8872710.1371/journal.pone.0088727Metabolomic heterogeneity of pulmonary arterial hypertension.Yidan ZhaoJenny PengCatherine LuMichael HsinMarco MuraLicun WuLei ChuRicardo ZamelTiago MachucaThomas WaddellMingyao LiuShaf KeshavjeeJohn GrantonMarc de PerrotAlthough multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.http://europepmc.org/articles/PMC3923046?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yidan Zhao Jenny Peng Catherine Lu Michael Hsin Marco Mura Licun Wu Lei Chu Ricardo Zamel Tiago Machuca Thomas Waddell Mingyao Liu Shaf Keshavjee John Granton Marc de Perrot |
spellingShingle |
Yidan Zhao Jenny Peng Catherine Lu Michael Hsin Marco Mura Licun Wu Lei Chu Ricardo Zamel Tiago Machuca Thomas Waddell Mingyao Liu Shaf Keshavjee John Granton Marc de Perrot Metabolomic heterogeneity of pulmonary arterial hypertension. PLoS ONE |
author_facet |
Yidan Zhao Jenny Peng Catherine Lu Michael Hsin Marco Mura Licun Wu Lei Chu Ricardo Zamel Tiago Machuca Thomas Waddell Mingyao Liu Shaf Keshavjee John Granton Marc de Perrot |
author_sort |
Yidan Zhao |
title |
Metabolomic heterogeneity of pulmonary arterial hypertension. |
title_short |
Metabolomic heterogeneity of pulmonary arterial hypertension. |
title_full |
Metabolomic heterogeneity of pulmonary arterial hypertension. |
title_fullStr |
Metabolomic heterogeneity of pulmonary arterial hypertension. |
title_full_unstemmed |
Metabolomic heterogeneity of pulmonary arterial hypertension. |
title_sort |
metabolomic heterogeneity of pulmonary arterial hypertension. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. |
url |
http://europepmc.org/articles/PMC3923046?pdf=render |
work_keys_str_mv |
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