Prostaglandin J2 Family and the Cardiovascular System
Abstract:Prostaglandins (PGs) of the J2 family including PGJ2, Δ12-PGJ2, and 15-deoxy-Δ12,14- PGJ2 (15d-PGJ2) are naturally occurring metabolites of PGD2. Among them, 15d-PGJ2 is a powerful ligand for the peroxisome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 and synthetic PPARγ ligands have been reported to exert several effects on vascular cells, such as antiproliferative, differentiation-inducing, anti-apoptotic, and anti-inflammatory effects, most of which seem to be atheroprotective, although PPARγ-independent mechanisms may be involved. Vascular endothelial cells, intimal smooth muscle cells, and cardiomyocytes express lipocalintype PGD synthase (L-PGDS) in vivo, which catalyzes the isomeric conversion of PGH2 to PGD2. L-PGDS expression in endothelial cells is stimulated by laminar fluid shear stress. PGD2 and 15d-PGJ2 are detected in the culture medium of endothelial cells exposed to shear stress. Serum and urinary levels of L-PGDS increase in diseases with vascular injuries, such as hypertension and diabetes. Based on these findings, we hypothesize that PGs of the J2 series are physiological substances produced in the vascular wall to protect vascular cells from injurious stimuli and to repress inflammatory reactions. If this hypothesis is correct, PGJ2 family members or other similar substances may provide novel preventive and therapeutic strategies for the treatment of vascular diseases.
Document Type: Review Article
Affiliations: Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Publication date: 2004-04-01
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- Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.
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