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J Biol Chem. 1999 Jun 11;274(24):17042-8.

Endothelial cell apoptosis induced by the peroxisome proliferator-activated receptor (PPAR) ligand 15-deoxy-Delta12, 14-prostaglandin J2.

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Center for Vascular Biology, Department of Physiology, University of Connecticut Health Center, Farmington, Connecticut 06030-3505, USA.


15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a bioactive prostanoid produced by dehydration and isomerization of PGD2, a cyclooxygenase product. It was recently shown to activate the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma), a critical transcription factor involved in adipocyte and monocyte differentiation. In this report, we show that 15d-PGJ2 is a potent inducer of caspase-mediated endothelial cell apoptosis. PPARalpha, -delta, and -gamma were expressed by endothelial cells, which, when treated with 15d-PGJ2, induced receptor translocation into the nucleus, and an increase in PPAR response element-driven reporter gene expression. Ciglitizone, a selective activator of PPARgamma, also induced transcriptional activation and endothelial cell apoptosis. Endothelial apoptosis induced by 15d-PGJ2 was inhibited by treatment of cells with an oligonucleotide decoy to a consensus PPAR response element sequence. Furthermore, overexpression of the PPARgamma isotype induced endothelial cell apoptosis, which was further potentiated by 15d-PGJ2 treatment. We conclude that 15d-PGJ2 induces endothelial cell apoptosis via a PPAR-dependent pathway. The PPAR pathway may be a therapeutic target for numerous pathologies in which excessive angiogenesis is implicated.

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