Fluid shear stress induces lipocalin-type prostaglandin D-2 synthase expression in vascular endothelial cells

Ligands for peroxisome proliferator-activated receptor gamma, such as the t hiazolidinedione class of antidiabetic drugs and 15-deoxy-Delta(12,14)-pros taglandin J(2) (15d-PGJ(2)), modulate various processes in atherogenesis. I n search of cells that generate prostaglandin D-2 (PGD(2)), the metabolic p recursor of 15d-PGJ(2), we identified PGD(2) from culture medium of endothe lial cells, To study how PGD(2) production is regulated in endothelial cell s, we investigated the role of fluid shear stress in the metabolism of PGD( 2). Endothelial cells expressed the mRNA for the lipocalin-type PGD(2) synt hase (L-PGDS) both in vitro and in vivo. Loading laminar shear stress using a parallel-plate flow chamber markedly enhanced the gene expression of L-P GDS, with the maximal effect being obtained at 15 to 30 dyne/cm(2). The exp ression began to increase within 6 hours after loading shear stress and rea ched the maximal level at 18 to 24 hours. In contrast, shear stress did not alter the expression levels of PGI(2) synthase and thromboxane A(2) syntha se. In parallel with the increase in the expression level of L-PGDS, endoth elial cells released PGD(2) and 15d-PGJ(2) into culture medium. These resul ts demonstrate that shear stress promotes PGD(2) production by stimulating L-PGDS expression and suggest the possibility that a peroxisome proliferato r-activated receptor gamma ligand is produced in vascular wall in response to blood flow.