The authors declare that they have no competing interests.
SZ and CW had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. SZ: contributed to the study design, data acquisition and collection; sample collection and biomarkers measurement; data analysis and interpretation, and manuscript preparation and revision. TY and XX: contributed to the study design; data analysis and interpretation; and manuscript preparation, revision, and approval of the final version. MW: contributed to the method establishment and evaluation; biomarkers measurement; and manuscript preparation, revision, and approval of the final version. LZ: contributed to the method establishment and evaluation; data acquisition and collection; sample collection and biomarkers measurement; and data analysis, and approval of the final version. YY: contributed to the study design; patients enrollment and assessment; data interpretation; and manuscript preparation, revision, and approval of the final version. ZZ: contributed to the study design; patients enrollment and assessment; data interpretation; and manuscript preparation, revision, and approval of the final version. FX: contributed to the study design; data analysis and interpretation; and manuscript preparation, revision, and approval of the final version. CW: contributed to the study design; data interpretation; and manuscript preparation, revision, and approval of the final version. All authors read and approved the final manuscript.
Oxidative stress (OS) and reduced nitric oxide (NO) bioavailability contribute to the pathogenesis of pulmonary hypertension (PH). Whether there are associations between OS and NO signaling biomarkers and whether these biomarkers are associated with the severity of PH remain unclear.
Blood samples were collected from 35 healthy controls and 35 patients with pulmonary arterial hypertension (PAH, n = 12) or chronic thromboembolic pulmonary hypertension (CTEPH, n = 23). The mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRI) were measured by right heart catheterization. We measured the derivative of reactive oxygen molecules (d-ROMs), biological antioxidant potential (BAP) and superoxide dismutase (SOD) by automatic biochemical analyzer, malondialdehyde (MDA) and asymmetric dimethylarginine (ADMA) by enzyme-linked immunosorbent assay. The relationship between oxidative-antioxidative biomarkers and ADMA, as well as their association with pulmonary hemodynamics, were analyzed.
Compared with age- and gender-matched controls, there was no significant difference of d-ROMs in PAH and CTEPH patients; MDA was increased in CTEPH patients (P = 0.034); BAP and SOD were decreased in PAH (P = 0.014, P < 0.001) and CTEPH patients (P = 0.015, P < 0.001); ADMA level was significantly higher in PAH (P = 0.007) and CTEPH patients (P < 0.001). No association between oxidative-antioxidative biomarkers and ADMA was found. Serum ADMA concentration was correlated with mPAP (r = 0.762, P = 0.006) and PVRI (r = 0.603, P = 0.038) in PAH patients.
The antioxidative potential and NO signaling are impaired in PAH and CTEPH. Increased serum ADMA level is associated with unfavorable pulmonary hemodynamics in PAH patients. Thus, ADMA may be useful in the severity evaluation and risk stratification of PAH.
Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009;30(20):2493–537. CrossRefPubMed
Karuppiah K, Druhan LJ, Chen CA, Smith T, Zweier JL, Sessa WC, et al. Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism. Am J Physiol Lung Cell Mol Physiol. 2011;301(3):H903–11. CrossRef
Birukov KG. Cyclic stretch, reactive oxygen species, and vascular remodeling. Antioxid Redox Signaling. 2009;11(7):1651–67. CrossRef
DeMarco VG, Habibi J, Whaley-Connell AT, Schneider RI, Heller RL, Bosanquet JP, et al. Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat. Am J Physiol Lung Cell Mol Physiol. 2008;294(6):H2659–68. CrossRef
Rawat DK, Alzoubi A, Gupte R, Chettimada S, Watanabe M, Kahn AG, et al. Increased reactive oxygen species, metabolic maladaptation, and autophagy contribute to pulmonary arterial hypertension-induced ventricular hypertrophy and diastolic heart failure. Hypertension. 2014;64(6):1266–74. CrossRefPubMed
Villegas LR, Kluck D, Field C, Oberley-Deegan RE, Woods C, Yeager ME, et al. Superoxide dismutase mimetic, MnTE-2-PyP, attenuates chronic hypoxia-induced pulmonary hypertension, pulmonary vascular remodeling, and activation of the NALP3 inflammasome. Antioxid Redox Signaling. 2013;18(14):1753–64. CrossRef
Cooke JP. ADMA: its role in vascular disease. Vascular medicine (London, England). 2005;10 Suppl 1:S11–7. CrossRef
Komatsu F, Kudoh H, Kagawa Y. Evaluation of oxidative stress and effectiveness of low-dose glucocorticoid therapy on exacerbation of chronic obstructive pulmonary disease. J Gerontol A: Biol Med Sci. 2007;62(4):459–64. CrossRef
Ismail M, Hossain MF, Tanu AR, Shekhar HU. Effect of spirulina intervention on oxidative stress, antioxidant status, and lipid profile in chronic obstructive pulmonary disease patients. BioMed research international 2015. 2015;2314-6141(Electronic):486120.
Margaritelis NV, Veskoukis AS, Paschalis V, Vrabas IS, Dipla K, Zafeiridis A, et al. Blood reflects tissue oxidative stress: a systematic review. Biomarkers: biochemical indicators of exposure, response, and susceptibility to chemicals. 2015;1366-5804(Electronic):1–12.
Manea A, Simionescu M. Nox enzymes and oxidative stress in atherosclerosis. Front Biosci (Schol Ed). 2012;4:651–70.
Markoulis N, Gourgoulianis KI, Moulas A, Gerogianni E, Molyvdas AP. Reactive oxygen metabolites as an index of chronic obstructive pulmonary disease severity. Panminerva Med. 2006;48(4):209–13. PubMed
Naruse R, Suetsugu M, Terasawa T, Ito K, Hara K, Takebayashi K, et al. Oxidative stress and antioxidative potency are closely associated with diabetic retinopathy and nephropathy in patients with type 2 diabetes. Saudi Med J. 2013;34(2):135–41. PubMed
Archer SL, Marsboom G, Kim GH, Zhang HJ, Toth PT, Svensson EC, et al. Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target. Circulation. 2010;121(24):2661–71. CrossRefPubMedPubMedCentral
Plicner D, Mazur P, Sadowski J, Undas A. Asymmetric dimethylarginine and oxidative stress following coronary artery bypass grafting: associations with postoperative outcome. European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery. 2014;45(5):e136–41. CrossRef
Pullamsetti S, Kiss L, Ghofrani HA, Voswinckel R, Haredza P, Klepetko W, et al. Increased levels and reduced catabolism of asymmetric and symmetric dimethylarginines in pulmonary hypertension. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2005;19(9):1175–7.
Houston M, Estevez A, Chumley P, Aslan M, Marklund S, Parks DA, et al. Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide-dependent signaling The Journal of biological chemistry. 1999;274(8):4985–94. PubMed
- Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study
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