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 thiazolidinedione class of antidiabetic drugs and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), modulate various processes in atherogenesis. In search of cells that generate prostaglandin D(2) (PGD(2)), the metabolic precursor of 15d-PGJ(2), we identified PGD(2) from culture medium of endothelial cells. To study how PGD(2) production is regulated in endothelial cells, 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) synthase (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-PGDS, with the maximal effect being obtained at 15 to 30 dyne/cm(2). The expression began to increase within 6 hours after loading shear stress and reached 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) synthase. In parallel with the increase in the expression level of L-PGDS, endothelial cells released PGD(2) and 15d-PGJ(2) into culture medium. These results demonstrate that shear stress promotes PGD(2) production by stimulating L-PGDS expression and suggest the possibility that a peroxisome proliferator-activated receptor gamma ligand is produced in vascular wall in response to blood flow.
Taba
Y
Y
Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan.
Sasaguri
T
T
Miyagi
M
M
Abumiya
T
T
Miwa
Y
Y
Ikeda
T
T
Mitsumata
M
M
D001158:Arteries / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D054834:Lipocalins; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000096:biosynthesis; D013314:Stress, Mechanical
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D003470:Culture Media; D054834:Lipocalins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2