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

Ling-yun Chu; Jun-Yang Liou; Kenneth K Wu

doi:10.1016/j.prostaglandins.2015.04.006

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

Prostaglandins Other Lipid Mediat. 2015 Apr-Jun:118-119:19-27. doi: 10.1016/j.prostaglandins.2015.04.006. Epub 2015 Apr 21.

Authors

Ling-yun Chu¹, Jun-Yang Liou², Kenneth K Wu³

Affiliations

¹ Metabolomic Medicine Research Center, China Medical University, Taichung, Taiwan.
² Metabolomic Medicine Research Center, China Medical University, Taichung, Taiwan; Institute of Cell and System Medicine, National Health Research Institute, Chunan, Taiwan.
³ 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.

PMID: 25910681
DOI: 10.1016/j.prostaglandins.2015.04.006

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.

Keywords: 14-3-3; PPAR; Prostacyclin.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

14-3-3 Proteins / metabolism*
Animals
Endothelial Cells / physiology
Endothelium, Vascular / physiology
Epoprostenol / physiology*
Humans
Muscle, Smooth, Vascular / cytology
Myocytes, Smooth Muscle / physiology
Peroxisome Proliferator-Activated Receptors / metabolism*
Platelet Aggregation
Protective Factors
Signal Transduction

Substances

14-3-3 Proteins
Peroxisome Proliferator-Activated Receptors
Epoprostenol