Asymmetric dimethyl arginine induces pulmonary vascular dysfunction via activation of signal transducer and activator of transcription 3 and stabilization of hypoxia-inducible factor 1-alpha

0455893 - BFÚ 2016 RIV CZ eng J - Journal Article
Pekarová, Michaela - Koudelka, Adolf - Kolářová, Hana - Ambrožová, Gabriela - Klinke, A. - Černá, A. - Kadlec, J. - Trundová, Mária - Šindlerová, Lenka - Kuchta, R. - Kuchtová, Z. - Lojek, Antonín - Kubala, Lukáš
Asymmetric dimethyl arginine induces pulmonary vascular dysfunction via activation of signal transducer and activator of transcription 3 and stabilization of hypoxia-inducible factor 1-alpha.
Vascular Pharmacology. Roč. 73, OCT 2015 (2015), s. 138-148. ISSN 1537-1891. E-ISSN 1879-3649
R&D Projects: GA ČR(CZ) GP13-40882P; GA MŠMT(CZ) EE2.3.30.0030
Grant - others:GAAV(CZ) M200041208
Institutional support: RVO:68081707
Keywords : NITRIC-OXIDE PRODUCTION * SMOOTH-MUSCLE-CELLS * ARTERIAL-HYPERTENSION
Subject RIV: BO - Biophysics; EI - Biotechnology ; Bionics (BTO-N)
Impact factor: 2.500, year: 2015

Pulmonary hypertension (PH), associated with imbalance in vasoactive mediators and massive remodeling of pulmonary vasculature, represents a serious health complication. Despite the progress in treatment, PH patients typically have poor prognoses with severely affected quality of life. Asymmetric dimethyl arginine (ADMA), endogenous inhibitor of endothelial nitric oxide synthase (eNOS), also represents one of the critical regulators of pulmonary vascular functions. The present study describes a novel mechanism of ADMA-induced dysfunction in human pulmonary endothelial and smooth muscle cells. The effect of ADMA was compared with well-established model of hypoxia-induced pulmonary vascular dysfunction. It was discovered for the first time that ADMA induced the activation of signal transducer and activator of transcription 3 (STAT3) and stabilization of hypoxia inducible factor la (HIF-1 alpha) in both types of cells, associated with drastic alternations in normal cellular functions (e.g., nitric oxide production, cell proliferation/Ca2+ concentration, production of pro-inflammatory mediators, and expression of eNOS, DDAH1, and ICAM-1).
Permanent Link: http://hdl.handle.net/11104/0256499