title: Metabolomic heterogeneity of pulmonary arterial hypertension.
abstract: 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.
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jenny
authors.initials: J
authors.lastname: Peng
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lu
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsin
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marco
authors.initials: M
authors.lastname: Mura
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Licun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Chu
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Zamel
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tiago
authors.initials: T
authors.lastname: Machuca
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Waddell
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Granton
authors.affiliation: Latner Thoracic Surgery Research Laboratories and Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
mesh_terms: D000328:Adult; D002952:Citric Acid Cycle; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006019:Glycolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D011651:Pulmonary Artery / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D005227:Fatty Acids