Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline
Abstract Background Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluat...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Respiratory Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12931-018-0800-5 |
| _version_ | 1828759987861585920 |
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| author | Hai-Kuo Zheng Jun-Han Zhao Yi Yan Tian-Yu Lian Jue Ye Xiao-Jian Wang Zhe Wang Zhi-Cheng Jing Yang-Yang He Ping Yang |
| author_facet | Hai-Kuo Zheng Jun-Han Zhao Yi Yan Tian-Yu Lian Jue Ye Xiao-Jian Wang Zhe Wang Zhi-Cheng Jing Yang-Yang He Ping Yang |
| author_sort | Hai-Kuo Zheng |
| collection | DOAJ |
| description | Abstract Background Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. Method A single subcutaneous injection of monocrotaline (MCT) (60 mg kg− 1) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. Results Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. Conclusion The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile. |
| first_indexed | 2024-12-11T01:07:00Z |
| format | Article |
| id | doaj.art-ca5822190fed461ebf2416b356d1412e |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-11T01:07:00Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-ca5822190fed461ebf2416b356d1412e2022-12-22T01:26:09ZengBMCRespiratory Research1465-993X2018-05-0119111210.1186/s12931-018-0800-5Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotalineHai-Kuo Zheng0Jun-Han Zhao1Yi Yan2Tian-Yu Lian3Jue Ye4Xiao-Jian Wang5Zhe Wang6Zhi-Cheng Jing7Yang-Yang He8Ping Yang9Department of Cardiology, China–Japan Union Hospital of Jilin UniversityState Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesState Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesState Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesState Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesState Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical SciencesState Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesState Key Laboratory of Cardiovascular Disease, FuWai Hospital, and Key Laboratory of Pulmonary Vascular Medicine, Peking Union Medical College and Chinese Academy of Medical SciencesDepartment of Cardiology, China–Japan Union Hospital of Jilin UniversityAbstract Background Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. Method A single subcutaneous injection of monocrotaline (MCT) (60 mg kg− 1) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. Results Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. Conclusion The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile.http://link.springer.com/article/10.1186/s12931-018-0800-5Pulmonary arterial hypertensionMetabolomicsUrea cyclePathwayBiomarker |
| spellingShingle | Hai-Kuo Zheng Jun-Han Zhao Yi Yan Tian-Yu Lian Jue Ye Xiao-Jian Wang Zhe Wang Zhi-Cheng Jing Yang-Yang He Ping Yang Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline Respiratory Research Pulmonary arterial hypertension Metabolomics Urea cycle Pathway Biomarker |
| title | Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline |
| title_full | Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline |
| title_fullStr | Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline |
| title_full_unstemmed | Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline |
| title_short | Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline |
| title_sort | metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline |
| topic | Pulmonary arterial hypertension Metabolomics Urea cycle Pathway Biomarker |
| url | http://link.springer.com/article/10.1186/s12931-018-0800-5 |
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