Shun Chen, Shujia Lin, Wei Liu, Qiuping Lin, Yi Yang, Qingzhu Qiu, Yanfang Zong, Tingting Xiao, Cuilan Hou, Lijian Xie
Shanghai Children’s Hospital and Shanghai Jiao Tong University School of Medicine. NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology. JinShan Hospital and Fudan University.
China
Frontiers in Bioscience Landmark Edition
Front Biosci (Landmark Ed) 2023; 28:
DOI: 10.31083/j.fbl2810251
Abstract
Background: Inhibition of fatty acid synthase (FAS) plays a crucial protective role in pulmonary hypertension (PH). Our aim was to identify novel metabolites in mice with hypoxia-induced PH after treatment with C75 (FAS inhibitor) and to confirm the presence of these metabolites in paediatric patients with PH.
Methods: The PH mouse model was built by chronic hypoxia and ovalbumin (OVA) assistance. Untargeted metabolomics was used to analyse mouse serum. Six children with PH and six relative controls (patients without lung and heart disease) were selected in Shanghai Children’s Hospital and they all performed blood tandem mass spectrometry during hospitalization.
Results: First, a total of 29 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified as differential metabolites in the hypoxia group compared with the control group. After C75 treatment, symptoms were partially relieved in the PH mouse, and 15 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified in the hypoxia + C75 group compared with the hypoxia group. These differential metabolites were enriched in arginine and glycerolipid metabolism through metabolite set enrichment analyses and were involved in excessive cell proliferation, which was a characteristic of PH. Second, glutamine and caproyl carnitine levels were increased in paediatric patients with PH.
Conclusions: FAS may be a potential PH therapeutic target. Lipid metabolites, polyamine, and glutamine, are closely related to PH. Putrescine and glutamine might be biomarkers for PH.
Category
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Animal Models of Pulmonary Vascular Disease and Therapy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes