Schematic representation of high glucose and palmitate-induced endothelial cell activation and dysfunction modulated in part by P2X7 and P2X4.

<p>Exposure of HUVECs to high glucose and palmitate results in the activation of the P2X7 and P2X4 causing (i) increased intracellular ROS and reduced eNOS contributing to endothelial cell dysfunction, and (ii) increased expression of IL-6, ICAM-1, VCAM-1, IL-8, and COX-2 resulting in endothelial cell activation. Blocking the P2X7 and P2X4 with AZ11645373 and PSB-12253, respectively, had a partial inhibitory effect on ROS as well as the inflammatory molecules with decreased leukocyte adhesion and vascular permeability. This is suggestive of the possible roles for P2X7 and P2X4 in modulating high glucose and palmitate-induced endothelial cell dysfunction, an early determinant of vascular disease.