Distinct regulation of vascular endothelial growth factor in intact human conduit vessels exposed to laminar fluid shear stress and pressure.
VEGF is a potent angiogenic factor. We tested the hypothesis that biomechanical forces may regulate VEGF expression. By using a computerized perfusion system, human umbilical veins were exposed to high/low shear stress or intraluminal pressure (25/4 dyn/cm(2) or 40/20 mmHg) for 1.5, 3, or 6 h. Quantification of VEGF gene expression was performed with real-time RT-PCR. VEGF protein was characterized by quantitative immunohistochemistry. All perfusion experiments were performed under identical pH, PO(2), and temperature. Shear stress induced significant biphasic regulation pattern of VEGF (P = 0.0044) with significant downregulation by 45 and 40% after 1.5 and 6 h perfusion, respectively (P = 0.006 and P = 0.0002). The temporal changes of the gene expression were accompanied by synchronal changes at the protein level. High pressure induced transient 25% downregulation of VEGF gene expression after 1.5 h perfusion (P = 0.031). These data provide the first evidence on modulating effects of biomechanical forces on the vascular angiogenic property.
Gan
L
L
Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden.
Miocic
M
M
Doroudi
R
R
Selin-Sjögren
L
L
Jern
S
S
D001794:Blood Pressure; D003201:Computers; D015536:Down-Regulation; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D010477:Perfusion; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013997:Time Factors; D014471:Umbilical Veins / Q000378:metabolism* / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors