title: Effects of shear stress on eicosanoid gene expression and metabolite production in vascular endothelium as studied in a novel biomechanical perfusion model.
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.
authors.affiliation: Clinical Experimental Research Laboratory, Heart and Lung Institute, Sahlgrenska University Hospital/Ostra, Göteborg University, Göteborg, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Doroudi
authors.forename: L M
authors.initials: LM
authors.lastname: Gan
authors.forename: L
authors.initials: L
authors.lastname: Selin Sjögren
authors.forename: S
authors.initials: S
authors.lastname: Jern
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D001483:Base Sequence; D001696:Biomechanical Phenomena; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000235:genetics; D015777:Eicosanoids / Q000235:genetics* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D008955:Models, Cardiovascular; D010477:Perfusion; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000235:genetics; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D017931:DNA Primers; D015777:Eicosanoids; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase