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Endothelial aquaporins and hypomethylation potential implications for atherosclerosis and cardiovascular disease
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Orientador(es)
Resumo(s)
Aquaporins (AQPs) are transmembrane channels that facilitate water and glycerol permeation through cell membranes. Recently, the water channel AQP1 was suggested to contribute to endothelial homeostasis and cardiovascular health. Less is known about endothelial aquaglyceroporins expression and its implication in cardiovascular disease (CVD). We have previously used cultured human endothelial cells under a hypomethylating environment to study endothelial dysfunction and activation, a phenotype implicated in the establishment of atherosclerosis and CVD. Here, we used the same cell model to investigate aquaporin’s expression and function in healthy or pro-atherogenic phenotype. We first confirmed key features of endothelium dysfunction and activation in our cell model, including an augmented endothelial transmigration under hypomethylation. Subsequently, we found AQP1 and AQP3 to be the most predominant AQPs accounting for water and glycerol fluxes, respectively, in the healthy endothelium. Moreover, endothelial hypomethylation led to decreased levels of AQP1 and impaired water permeability without affecting AQP3 and glycerol permeability. Furthermore, TNF-α treatment-induced AQP1 downregulation suggesting that the inflammatory NF-κB signaling pathway mediates AQP1 transcriptional repression in a pro-atherogenic endothelium, a possibility that warrants further investigation. In conclusion, our results add further support to AQP1 as a candidate player in the setting of endothelial dysfunction and CVD.
Descrição
We thank Fundacao para a Ciencia e Tecnologia, Portugal, for financial support through the project grants PTDC/SAU-ORG/112683/2009 and UID/DTP/04138/2013 (iMed.ULisboa) and PhD fellowships PD/BD/113634/2015 (Ines Vieira da Silva) and SFRH/BD/73021/2010 (Madalena Barroso).
Palavras-chave
Aquaporins Endothelial dysfunction Hypomethylation S-adenosylhomocysteine Water and glycerol permeability Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry SDG 3 - Good Health and Well-being