Transcriptional and posttranscriptional regulation of cyclooxygenase-2 expression by fluid shear stress in vascular endothelial cells

Hiroyasu Inoue, Yoji Taba, Yoshikazu Miwa, Chiaki Yokota, Megumi Miyagi, Toshiyuki Sasaguri

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)

Abstract

Objective - Fluid shear stress induces cyclooxygenase (COX)-2 gene expression in vascular endothelial cells. We investigated the underlying mechanism of this induction. Methods and Results - Exposure of human umbilical vein endothelial cells to laminar shear stress in the physiological range (1 to 30 dyne/cm2) upregulated the expression of COX-2 but not COX-1, a constitutive isozyme of COX. The expression of COX-2 mRNA began to increase within 0.5 hour after the loading of shear stress and reached a maximal level at 4 hours. Roles of the promoter region and the 3′-untranslated region in the human COX-2 gene were evaluated by the transient transfection of luciferase reporter vectors into bovine arterial endothelial cells. Shear stress elevated luciferase activity via the region between -327 and 59 bp. Mutation analysis indicated that cAMP-responsive element (-59/-53 bp) was mainly involved in this response. On the other hand, shear stress selectively stabilized COX-2 mRNA. Moreover, shear stress elevated luciferase activity when a 3′-untranslated region of COX-2 gene containing 17 copies of the AUUUA mRNA instability motif was inserted into the vector. Conclusions - Transcriptional activation and posttranscriptional mRNA stabilization contribute to the rapid and sustained expression of COX-2 in response to shear stress.

Original languageEnglish
Pages (from-to)1415-1420
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 2002

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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