title: Profiling nitric oxide metabolites in patients with idiopathic pulmonary arterial hypertension.
abstract: Intact nitric oxide (NO) signalling is critical to maintaining appropriate pulmonary vascular tone. NO bioavailability is reduced in patients with pulmonary arterial hypertension. This study aimed to examine the impact of NO plasma metabolites (NOx) relative to haemodynamic dysfunction and mortality in patients with idiopathic pulmonary arterial hypertension (IPAH).A total of 104 consecutive adult IPAH patients who had undergone genetic counselling when first diagnosed were enrolled in this prospective study.The median concentration of NOx (μmol·L-1) was significantly lower in IPAH patients compared with healthy subjects, and was decreased further in 19 carriers of the bone morphogenetic protein-receptor type-2 (BMPR2) mutation compared to non-carriers. Reduced concentrations of NOx were correlated with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. Compared with higher baseline NOx concentrations, patients with a NOx concentration of ≤10 μmol·L-1had a markedly worse survival. After adjustment for clinical features, a BMPR2 mutation and haemodynamics, a lower NOx level remained an increased risk of mortality.Patients with IPAH had lower levels of plasma NOx, which correlated inversely with mPAP, PVR and survival. Plasma NOx may be an important biomarker and prognostic indicator, suggesting that reduced NO synthesis contributes to the pathogenesis of IPAH.
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.|Both authors contributed equally.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.|Both authors contributed equally.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Hong-Da
authors.initials: HD
authors.lastname: Zhang
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Sun
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qin-Hua
authors.initials: QH
authors.lastname: Zhao
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Liu
authors.affiliation: Dept of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China jingzhicheng@vip.163.com.|State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy Medical Science, Beijing, China.
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics; D006328:Cardiac Catheterization; D002302:Cardiac Output; D065627:Familial Primary Pulmonary Hypertension / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005817:Genetic Counseling; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism*; D011312:Pressure; D011379:Prognosis; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000473:pathology; D012306:Risk; D014655:Vascular Resistance; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II