Distinct regulation of vascular endothelial growth factor in intact human conduit vessels exposed to laminar fluid shear stress and pressure

Biochem Biophys Res Commun. 2000 Jun 7;272(2):490-6. doi: 10.1006/bbrc.2000.2663.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Pressure
  • Computers
  • Down-Regulation
  • Endothelial Growth Factors / genetics*
  • Endothelial Growth Factors / metabolism
  • Endothelium, Vascular / metabolism
  • Gene Expression Regulation*
  • Hemodynamics*
  • Humans
  • Immunohistochemistry
  • Lymphokines / genetics*
  • Lymphokines / metabolism
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism
  • Perfusion
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Mechanical
  • Time Factors
  • Umbilical Veins / metabolism*
  • Umbilical Veins / physiology*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors