title: Prostacyclin protects vascular integrity via PPAR/14-3-3 pathway.
abstract: 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 (PGI2). PGI2 is known to inhibit platelet aggregation and controls smooth muscle cell contraction via IP receptors. Recent studies indicate that PGI2 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 14-3-3ɛ or 14-3-3β enhances binding and sequestration of Akt-mediated phosphorylated Bad and reduces Bad-mediated apoptosis via the mitochondrial pathway. Experimental data indicate that administration of PGI2 analogs or augmentation of PGI2 production by gene transfer attenuates endothelial damage and organ infarction caused by ischemia-reperfusion injury. The protective effect of PGI2 is attributed in part to preserving endothelial integrity.
authors.affiliation: Metabolomic Medicine Research Center, China Medical University, Taichung, Taiwan.
authors.forename: Ling-yun
authors.initials: LY
authors.lastname: Chu
authors.affiliation: Metabolomic Medicine Research Center, China Medical University, Taichung, Taiwan; Institute of Cell and System Medicine, National Health Research Institute, Chunan, Taiwan.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Liou
authors.affiliation: Metabolomic Medicine Research Center, China Medical University, Taichung, Taiwan; Institute of Cell and System Medicine, National Health Research Institute, Chunan, Taiwan; Department of Medical Sciences, National Tsing-Hua University, Hsin-chu, Taiwan. Electronic address: kkgo@nhri.org.tw.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Wu
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010974:Platelet Aggregation; D065840:Protective Factors; D015398:Signal Transduction
chemical_list: D048948:14-3-3 Proteins; D047492:Peroxisome Proliferator-Activated Receptors; D011464:Epoprostenol
keywords: 14-3-3; PPAR; Prostacyclin