Effects of shear stress on eicosanoid gene expression and metabolite production in vascular endothelium as studied in a novel biomechanical perfusion model.

S Jern, R Doroudi, L M Gan, L Selin Sjögren

Journal: Biochemical and biophysical research communications 2000;269(1):257-64

PMID: 10694510

Full Text on Elsevier Science View on PubMed

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 (PGI(2)) and thromboxane A(2) (TXA(2)) in endothelium of intact conduit vessels. Paired human umbilical veins were perfused at high/low shear stress (25/<4 dyn/cm(2)) 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(1alpha) and TXA(2) 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.

Address: Clinical Experimental Research Laboratory, Heart and Lung Institute, Sahlgrenska University Hospital/Ostra, Göteborg University, Göteborg, Sweden.

DOI: 10.1006/bbrc.2000.2279

Link outs

Free resources

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-PTGS2-1

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0006...

MeSH Terms: 6-Ketoprostaglandin F1 alpha, Base Sequence, Biomechanical Phenomena, Cyclooxygenase 1, Cyclooxygenase 2, DNA Primers, Eicosanoids, Endothelium, Vascular, Epoprostenol, Female, Gene Expression, Humans, In Vitro Techniques, Isoenzymes, Membrane Proteins, Models, Cardiovascular, Perfusion, Pregnancy, Prostaglandin-Endoperoxide Synthases, RNA, Messenger, Stress, Mechanical, Thromboxane A2, Thromboxane-A Synthase, Umbilical Veins