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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 ASEP 0455893 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title 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 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, ORCIDNumber of authors 13 Source Title Vascular Pharmacology. - : Elsevier - ISSN 1537-1891
Roč. 73, OCT 2015 (2015), s. 138-148Number of pages 11 s. Publication form Print - P Language eng - English Country CZ - Czech Republic Keywords NITRIC-OXIDE PRODUCTION ; SMOOTH-MUSCLE-CELLS ; ARTERIAL-HYPERTENSION Subject RIV BO - Biophysics Subject RIV - cooperation Institute of Biotechnology - Biotechnology ; Bionics R&D Projects GP13-40882P GA ČR - Czech Science Foundation (CSF) EE2.3.30.0030 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BFU-R - RVO:68081707 UT WOS 000362056600018 DOI 10.1016/j.vph.2015.06.005 Annotation 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). Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2016
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