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

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Ligands for peroxisome proliferator-activated receptor γ, such as the thiazolidinedione class of antidiabetic drugs and 15-deoxy-Δ12,14- 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 γ ligand is produced in vascular wall in response to blood flow.

Original languageEnglish
Pages (from-to)967-973
Number of pages7
JournalCirculation research
Volume86
Issue number9
DOIs
Publication statusPublished - May 12 2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

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