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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

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    SYSNO ASEP0455893
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleAsymmetric dimethyl arginine induces pulmonary vascular dysfunction via activation of signal transducer and activator of transcription 3 and stabilization of hypoxia-inducible factor 1-alpha
    Author(s) Pekarová, Michaela (BFU-R) RID
    Koudelka, Adolf (BFU-R) ORCID
    Kolářová, Hana (BFU-R) RID
    Ambrožová, Gabriela (BFU-R) RID
    Klinke, A. (DE)
    Černá, A. (CZ)
    Kadlec, J. (CZ)
    Trundová, Mária (BTO-N)
    Šindlerová, Lenka (BFU-R) RID, ORCID
    Kuchta, R. (CZ)
    Kuchtová, Z. (CZ)
    Lojek, Antonín (BFU-R) RID
    Kubala, Lukáš (BFU-R) RID, ORCID
    Number of authors13
    Source TitleVascular Pharmacology. - : Elsevier - ISSN 1537-1891
    Roč. 73, OCT 2015 (2015), s. 138-148
    Number of pages11 s.
    Publication formPrint - P
    Languageeng - English
    CountryCZ - Czech Republic
    KeywordsNITRIC-OXIDE PRODUCTION ; SMOOTH-MUSCLE-CELLS ; ARTERIAL-HYPERTENSION
    Subject RIVBO - Biophysics
    Subject RIV - cooperationInstitute of Biotechnology - Biotechnology ; Bionics
    R&D ProjectsGP13-40882P GA ČR - Czech Science Foundation (CSF)
    EE2.3.30.0030 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    Institutional supportBFU-R - RVO:68081707
    UT WOS000362056600018
    DOI10.1016/j.vph.2015.06.005
    AnnotationPulmonary 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).
    WorkplaceInstitute of Biophysics
    ContactJana Poláková, polakova@ibp.cz, Tel.: 541 517 244
    Year of Publishing2016
Number of the records: 1  

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