Effects of Shear Stress on Eicosanoid Gene Expression and Metabolite Production in Vascular Endothelium as Studied in a Novel Biomechanical Perfusion Model

doi:10.1006/bbrc.2000.2279

Biochemical and Biophysical Research Communications

Volume 269, Issue 1, 5 March 2000, Pages 257-264

https://doi.org/10.1006/bbrc.2000.2279 Get rights and content

Abstract

This study investigated the effects of shear stress on gene expression of prostacyclin synthesis-related enzymes cyclooxygenases (COX-1 and COX-2), prostacyclin synthase (PGS), and thromboxane synthase (TXS) and their metabolites prostaglandin (PGI₂) and thromboxane A₂ (TXA₂) in endothelium of intact conduit vessels. Paired human umbilical veins were perfused at high/low shear stress (25/<4 dyn/cm²) at identical intraluminal pressure (20 mmHg) for 1.5, 3, or 6 hours in a computerized vascular model. High shear perfusion induced a significant, monophasic upregulation of PGS and TXS gene expressions after 6 hours. COX-1 and COX-2 mRNA showed a biphasic response with peaks at 1.5 and 6 hours, with a nadir level at 3 hours. Shear-induced gene expression was associated with a significantly greater accumulation of 6-keto prostaglandin F_1α and TXA₂ in the perfusion medium. Thus, shear stress independently of perfusion pressure alters the expression of prostacyclin synthesis-related enzymes and the biosynthesis of their vasoactive metabolites.

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The nature of potential activating stimuli for COX-2 in human AAAs remains uncertain. COX-2 protein localized to lining endothelial cells of the tunica intima, which is consistent with fluid shear stress acting as a stimulus for COX-2 expression.21,22 We did not note any association between smoking habit and COX-2, although benzo[a]pyrene, a polycyclic aromatic hydrocarbon found in tobacco smoke, is recognized to induce COX-2 in vascular smooth muscle cells.23
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¹: To whom correspondence should be addressed at Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Östra, S-416 85 Göteborg, Sweden. Fax: +46-31-19 14 16. E-mail: [email protected].

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Regular ArticleEffects of Shear Stress on Eicosanoid Gene Expression and Metabolite Production in Vascular Endothelium as Studied in a Novel Biomechanical Perfusion Model

Abstract

J. Biol. Chem.

J. Vasc. Surg.

Biochem. Biophys. Res. Commun.

Eur. J. Vasc. Surg.

J. Surg. Res.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Am. J. Obstet. Gynecol.

Prostaglandins

J. Clin. Invest.

Prostaglandins

J. Biomech. Eng.

Trans. Am. Soc. Art. Intern. Org.

Science

Regular Article
Effects of Shear Stress on Eicosanoid Gene Expression and Metabolite Production in Vascular Endothelium as Studied in a Novel Biomechanical Perfusion Model