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(Circulation Research. 2000;86:967.)
© 2000 American Heart Association, Inc.

Cellular Biology

Fluid Shear Stress Induces Lipocalin-Type Prostaglandin D₂ Synthase Expression in Vascular Endothelial Cells

Yoji Taba, Toshiyuki Sasaguri, Megumi Miyagi, Takeo Abumiya, Yoshikazu Miwa, Toshiko Ikeda, Masako Mitsumata

From the Departments of Bioscience (Y.T., T.S., M. Miyagi, Y.M.) and Epidemiology (T.A.), National Cardiovascular Center Research Institute, Osaka; Third Department of Internal Medicine (Y.T., M. Miyagi), University of the Ryukyus School of Medicine, Okinawa; and Department of Pathology (T.I., M. Mitsumata), School of Medicine, Yamanashi Medical University, Yamanashi, Japan.

Correspondence to Toshiyuki Sasaguri, MD, PhD, Department of Bioscience, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. E-mail sasaguri{at}ri.ncvc.go.jp

Abstract—Ligands for peroxisome proliferator–activated receptor , such as the thiazolidinedione class of antidiabetic drugs and 15-deoxy-^12,14-prostaglandin J₂ (15d-PGJ₂), modulate various processes in atherogenesis. In search of cells that generate prostaglandin D₂ (PGD₂), the metabolic precursor of 15d-PGJ₂, we identified PGD₂ from culture medium of endothelial cells. To study how PGD₂ production is regulated in endothelial cells, we investigated the role of fluid shear stress in the metabolism of PGD₂. Endothelial cells expressed the mRNA for the lipocalin-type PGD₂ 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/cm². 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 PGI₂ synthase and thromboxane A₂ synthase. In parallel with the increase in the expression level of L-PGDS, endothelial cells released PGD₂ and 15d-PGJ₂ into culture medium. These results demonstrate that shear stress promotes PGD₂ production by stimulating L-PGDS expression and suggest the possibility that a peroxisome proliferator–activated receptor ligand is produced in vascular wall in response to blood flow.

Key Words: shear stress • vascular endothelial cells • prostaglandins

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