Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.
There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development...
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0150480&type=printable |
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| author | Olga Rafikova Mary L Meadows Jason M Kinchen Robert P Mohney Emin Maltepe Ankit A Desai Jason X-J Yuan Joe G N Garcia Jeffrey R Fineman Ruslan Rafikov Stephen M Black |
| author_facet | Olga Rafikova Mary L Meadows Jason M Kinchen Robert P Mohney Emin Maltepe Ankit A Desai Jason X-J Yuan Joe G N Garcia Jeffrey R Fineman Ruslan Rafikov Stephen M Black |
| author_sort | Olga Rafikova |
| collection | DOAJ |
| description | There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH. |
| format | Article |
| id | doaj-art-55c5de473c2c4faaa18587933f9f342c |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-55c5de473c2c4faaa18587933f9f342c2025-08-20T03:10:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015048010.1371/journal.pone.0150480Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.Olga RafikovaMary L MeadowsJason M KinchenRobert P MohneyEmin MaltepeAnkit A DesaiJason X-J YuanJoe G N GarciaJeffrey R FinemanRuslan RafikovStephen M BlackThere is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0150480&type=printable |
| spellingShingle | Olga Rafikova Mary L Meadows Jason M Kinchen Robert P Mohney Emin Maltepe Ankit A Desai Jason X-J Yuan Joe G N Garcia Jeffrey R Fineman Ruslan Rafikov Stephen M Black Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung. PLoS ONE |
| title | Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung. |
| title_full | Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung. |
| title_fullStr | Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung. |
| title_full_unstemmed | Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung. |
| title_short | Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung. |
| title_sort | metabolic changes precede the development of pulmonary hypertension in the monocrotaline exposed rat lung |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0150480&type=printable |
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