title: Intraluminal pressure modulates eicosanoid enzyme expression in vascular endothelium of intact human conduit vessels at physiological levels of shear stress.
abstract: OBJECTIVE
  Biosynthesis of eicosanoid metabolites in blood vessels regulates vascular tone and platelet function. We investigated whether intraluminal pressure modulates gene and protein expression of key eicosanoid enzymes in intact human conduit vessels and/or release of their vasoactive metabolites.
  
  
  METHODS
  Paired segments of human umbilical veins were perfused under laminar flow for 1.5, 3 and 6 h at high versus low intraluminal pressure (40/20 mmHg) with identical shear stress (10 dyn/cm(2)). Endothelial cell mRNAs encoding cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), prostaglandin synthase (PGS), and thromboxane synthase (TXS) were measured by quantitative real-time RT-PCR. Secretion of PGI2 and TXA2 to the perfusion medium was measured by enzyme immunoassay of their metabolites 6-keto-prostaglandin F(1alpha) and TXB2.
  
  
  RESULTS
  Intraluminal pressures were 39.9 +/- 0.02 and 20.0 +/- 0.03 mmHg (P < 0.0001) in high and low pressure circuits, and shear stress levels were 10.6 +/- 0.60 and 9.7 +/- 0.36 dyn/cm(2) (NS, not significant). COX-1 mRNA was significantly up-regulated after 1.5 h of high pressure stimulation and continued up to 3 h, but fell thereafter significantly below baseline after 6 h. COX-2 mRNA was initially significantly down-regulated, followed by a significant up-regulation after 6 h. Gene expressions of PGS and TXS were significantly induced after 6 h of high pressure perfusion. High pressure depressed the production of PGI(2) (P < 0.05) but did not alter TXA(2) formation.
  
  
  CONCLUSIONS
  Intraluminal pressure has differential effects on gene and protein expression of key eicosanoid enzymes and biosynthesis of prostanoid metabolites in intact human conduit vessels. The new, computerized biomechanical perfusion system may be a useful tool to elucidate specific effects of various biomechanical forces on intact mammalian conduit vessels.
authors.affiliation: Clinical Experimental Research Laboratory, Heart and Lung Institute, Sahlgrenska University Hospital/Ostra, Göteborg University, S-416 85 Göteborg, Sweden.
authors.forename: Roya
authors.initials: R
authors.lastname: Doroudi
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Gan
authors.forename: Lena Selin
authors.initials: LS
authors.lastname: Sjögren
authors.forename: Sverker
authors.initials: S
authors.lastname: Jern
mesh_terms: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015777:Eicosanoids / Q000096:biosynthesis* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D010477:Perfusion; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D013194:Staining and Labeling; D013314:Stress, Mechanical; D013930:Thromboxane-A Synthase / Q000096:biosynthesis; D013997:Time Factors; D014471:Umbilical Veins / Q000201:enzymology*; D015854:Up-Regulation / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D015777:Eicosanoids; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase