Aquaporins and hypomethylation in endothelia: Implications in cardiovascular disease

Aquaporins (AQPs) are a family of protein channels that facilitatethe transport of water and/or small solutes through cell mem-branes. The aquaglyceroporins (AQP3, 7, 9, 10) facilitate glycerolpermeation and are involved in glycerol metabolism being crucialfor energy production and homeostasis in different organs (liver,adipose tissue, muscle and heart). Recently, AQP1 was proposedto be involved in endothelial homeostasis and cardiovascularhealth, but the expression of endothelial aquaglyceroporins andtheir implication in cardiovascular disease (CVD) still remainsunclear. Human endothelial cells (HUVEC) cultured under ahypomethylating environment were shown to be a valuable modelto study endothelial dysfunction and activation, a phenotypeimplicated in the establishment of CVD. In this study, we used theHUVEC cell model to study the expression and function ofaquaglyceroporins in healthy or pro-atherogenic phenotype. Ourresults showed that, despite AQP5, 7 and 10 being detected, AQP1and AQP3 are the major AQPs accounting for water and glycerolfluxes, respectively, in the healthy endothelium. After confirmingthe key features of endothelium dysfunction and activation, wefound that hypomethylation leads to decreased levels of AQP1and impairs water permeability without affecting AQP3 and glyc-erol permeability. Moreover, TNF-a treatment induced AQP1downregulation suggesting that the inflammatory NF-jB signalingpathway mediates AQP1 transcriptional repression in a pro-atherogenic endothelium. Our results evidence AQP1 as a candi-date player in the setting of endothelial dysfunction and CVD.