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Schuoler, C; Haider, TJ; Leuenberger, C; Vogel, J; Ostergaard, L; Kwapiszewska, G; Kohler, M; Gassmann, M; Huber, LC; Brock, M.
Aquaporin 1 controls the functional phenotype of pulmonary smooth muscle cells in hypoxia-induced pulmonary hypertension.
Basic Res Cardiol. 2017; 112(3):30-30
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Kwapiszewska-Marsh Grazyna
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Abstract:
Vascular remodelling in hypoxia-induced pulmonary hypertension (PH) is driven by excessive proliferation and migration of endothelial and smooth muscle cells. The expression of aquaporin 1 (AQP1), an integral membrane water channel protein involved in the control of these processes, is tightly regulated by oxygen levels. The role of AQP1 in the pathogenesis of PH, however, has not been directly addressed so far. This study was designed to characterize expression and function of AQP1 in pulmonary vascular cells from human arteries and in the mouse model of hypoxia-induced PH. Exposure of human pulmonary vascular cells to hypoxia significantly induced the expression of AQP1. Similarly, levels of AQP1 were found to be upregulated in lungs of mice with hypoxia-induced PH. The functional role of AQP1 was further tested in human pulmonary artery smooth muscle cells demonstrating that depletion of AQP1 reduced proliferation, the migratory potential, and, conversely, increased apoptosis of these cells. This effect was associated with higher expression of the tumour suppressor gene p53. Using the mouse model of hypoxia-induced PH, application of GapmeR inhibitors targeting AQP1 abated the hypoxia-induced upregulation of AQP1 and, of note, reversed PH by decreasing both right ventricular pressure and hypertrophy back to the levels of control mice. Our data suggest an important functional role of AQP1 in the pathobiology of hypoxia-induced PH. These results offer novel insights in our pathogenetic understanding of the disease and propose AQP1 as potential therapeutic in vivo target.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Aquaporin 1 - metabolism
Blotting, Western -
Cells, Cultured -
Disease Models, Animal -
Humans -
Hypertension, Pulmonary - metabolism
Hypoxia -
Male -
Mice -
Mice, Inbred C57BL -
Muscle, Smooth, Vascular - metabolism
Myocytes, Smooth Muscle - metabolism
Phenotype -
Pulmonary Artery - metabolism
Real-Time Polymerase Chain Reaction -
Vascular Remodeling - physiology

Find related publications in this database (Keywords)
Aquaporin 1
Pulmonary hypertension
Hypoxia
Proliferation
Vascular remodelling
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