Endothelial Aquaporins and Hypomethylation: Potential Implications for Atherosclerosis and Cardiovascular Disease

Abstract

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.

Aquaporin-driven hydrogen peroxide transport: a case of molecular mimicry?

“…Previous studies reported the experimentally calculated permeability values for water and glycerol permeation via different AQPs, including AQP3, in different cells. 1,[24][25][26] Moreover, a few studies also included hydrogen peroxide transport rates via AQP3. 14,27 In general, permeability values for water are in the order of 10 À3 cm s À1 , while glycerol and H 2 O 2 are in the range of 10 À6 cm s À1 .…”

Conjugated polymers optically regulate the fate of endothelial colony-forming cells

“…The superoxide further evolves, leading to the generation of different ROS and, lastly, ending up with hydrogen peroxide production. It has been reported that extracellular H 2 O 2 can cross the plasma membrane through aquaporin AQP3, thereby triggering intracellular ROS signaling ( 47 , 48 ). In line with our previous results, we have demonstrated here that intracellular ROS enhancement does occur in ECFCs upon photoexcitation of polymer thin films, thus contributing to TRPV1 activation.…”

The Aquaporin-3-Inhibiting Potential of Polyoxotungstates

“…The relative quantification of gene expression was determined using the 2 Ct method based on a Livak method modification [62]. AQP gene expression was normalized to the mean of two housekeeping genes (HPRT-1 and β-actin) [63]. This procedure was performed in triplicate.…”