Prostacyclin protects vascular integrity via PPAR/14-3-3 pathway

Vascular integrity is protected by the lining endothelial cells (ECs) through structural and molecular protective mechanisms. In response to external stresses, ECs are dynamic in producing protective molecules such as prostacyclin (PGI(2)). PGI(2) is known to inhibit platelet aggregation and controls smooth muscle cell contraction via IP receptors. Recent studies indicate that PGI(2) defends endothelial survival and protects vascular smooth muscle cell from apoptosis via peroxisome-proliferator activated receptors (PPAR). PPAR activation results in 14-3-3 upregulation. Increase in cytosolic 14-3-3 epsilon or 14-3-3 beta enhances binding and sequestration of Akt-mediated phosphorylated Bad and reduces Bad-mediated apoptosis via the mitochondrial pathway. Experimental data indicate that administration of PGI(2) analogs or augmentation of PGI(2) production by gene transfer attenuates endothelial damage and organ infarction caused by ischemia-reperfusion injury. The protective effect of PGI(2) is attributed in part to preserving endothelial integrity. (C) 2015 Published by Elsevier Inc.