Protective Effects of 10-nitro-oleic Acid in a Hypoxia-Induced Murine Model of Pulmonary Hypertension

0431017 - BFÚ 2015 RIV US eng J - Journal Article
Klinke, A. - Moeller, A. - Pekarová, Michaela - Ravekes, T. - Friedrichs, K. - Berlin, M. - Scheu, K.M. - Kubala, Lukáš - Kolářová, Hana - Ambrožová, Gabriela - Schermuly, R.T. - Woodcock, S.R. - Freeman, B.A. - Rosenkranz, S. - Baldus, S. - Rudolph, V. - Rudolph, T.K.
Protective Effects of 10-nitro-oleic Acid in a Hypoxia-Induced Murine Model of Pulmonary Hypertension.
American Journal of Respiratory Cell and Molecular Biology. Roč. 51, č. 1 (2014), s. 155-162. ISSN 1044-1549. E-ISSN 1535-4989
R&D Projects: GA MŠMT(CZ) ED1.100/02/0123; GA ČR(CZ) GP13-40824P
Grant - others:GAAV(CZ) M200041208
Institutional support: RVO:68081707
Keywords : NITRO-FATTY ACIDS * MUSCLE-CELL PROLIFERATION * ARTERIAL-HYPERTENSION
Subject RIV: BO - Biophysics
Impact factor: 3.985, year: 2014

Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert potent anti-inflammatory effects. The current study investigated the role of 10-nitro-oleic acid (OA-NO2) in modulating the pathophysiology of PAH in mice. Mice were kept for 28 days under normoxic or hypoxic conditions, and OA-NO2 was infused subcutaneously. Right ventricular systolic pressure (RVPsys) was determined, and right ventricular and lung tissue was analyzed. The effect of OA-NO2 on cultured pulmonary artery smooth muscle cells (PASMCs) and macrophages was also investigated. Changes in RVPsys revealed increased pulmonary hypertension in mice on hypoxia, which was significantly decreased by OA-NO2 administration. Right ventricular hypertrophy and fibrosis were also attenuated by OA-NO2 treatment.
Permanent Link: http://hdl.handle.net/11104/0235680