Prostaglandin J₂ family and the cardiovascular system

Prostaglandins (PGs) of the J₂ family including PGJ₂, Δ¹²-PGJ₂, and 15-deoxy-Δ^12,14-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 anti-proliferative, 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 lipocalin-type 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.