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...
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SAGE Publishing
2021
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oai:doaj.org-article:f5f7b841688641029471487c81d6c33f2021-12-02T00:03:31ZMetabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension2045-894010.1177/20458940211054325https://doaj.org/article/f5f7b841688641029471487c81d6c33f2021-11-01T00:00:00Zhttps://doi.org/10.1177/20458940211054325https://doaj.org/toc/2045-8940Alterations 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.Samar FarhaSuzy ComhairYuan HouMargaret M. ParkJacqueline SharpLaura PetersonBelinda WillardRenliang ZhangFrank P. DiFilippoDonald NeumannW.H. Wilson TangFeixiong ChengSerpil ErzurumSAGE PublishingarticleDiseases of the circulatory (Cardiovascular) systemRC666-701Diseases of the respiratory systemRC705-779ENPulmonary Circulation, Vol 11 (2021) |
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DOAJ |
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Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the respiratory system RC705-779 |
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Diseases of the circulatory (Cardiovascular) system RC666-701 Diseases of the respiratory system RC705-779 Samar Farha Suzy Comhair Yuan Hou Margaret M. Park Jacqueline Sharp Laura Peterson Belinda Willard Renliang Zhang Frank P. DiFilippo Donald Neumann W.H. Wilson Tang Feixiong Cheng Serpil Erzurum Metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension |
| 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 |
article |
| author |
Samar Farha Suzy Comhair Yuan Hou Margaret M. Park Jacqueline Sharp Laura Peterson Belinda Willard Renliang Zhang Frank P. DiFilippo Donald Neumann W.H. Wilson Tang Feixiong Cheng Serpil Erzurum |
| author_facet |
Samar Farha Suzy Comhair Yuan Hou Margaret M. Park Jacqueline Sharp Laura Peterson Belinda Willard Renliang Zhang Frank P. DiFilippo Donald Neumann W.H. Wilson Tang Feixiong Cheng Serpil Erzurum |
| author_sort |
Samar Farha |
| title |
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_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_sort |
metabolic endophenotype associated with right ventricular glucose uptake in pulmonary hypertension |
| publisher |
SAGE Publishing |
| publishDate |
2021 |
| url |
https://doaj.org/article/f5f7b841688641029471487c81d6c33f |
| work_keys_str_mv |
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1718403960777211904 |