Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in normal and atherosclerotic human arteries

Am J Pathol. 1997 May;150(5):1673-85.


Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is an endothelial-cell-specific mitogen; as such, its role in angiogenesis has been studied extensively. VEGF/VPF may also serve as a local, endogenous regulator of large-vessel endothelial cell integrity. Surprisingly, however, VEGF/VPF expression in normal and/or atherosclerotic vessels has not been previously characterized. Accordingly, we studied normal human arteries and veins as well as atherosclerotic and restenotic human coronary arteries for evidence of VEGF/VPF expression. VEGF/VPF was detected immunohistochemically in sections of normal human aorta, mammary artery, and saphenous vein. Moreover, VEGF/ VPF expression was identified in 32 (97%) of 33 pathological coronary arterial specimens; the extent of VEGF/VPF staining was graded as moderate to strong in 21 of the 32 (66%) positive specimens. VEGF/VPF double immunostaining and in situ hybridization demonstrated that smooth muscle cells constitute the principal cellular source of VEGF/VPF. VEGF/VPF immunostaining among primary atherosclerotic lesions localized predominantly to the extracellular matrix. In restenotic specimens, VEGF/VPF immunostaining was more prominently cellular, particularly among proliferating smooth muscle cells. Although VEGF/VPF expression was observed in areas of macrophage infiltration, double immunostaining failed to localize VEGF/VPF to macrophages in these foci; instead, double immunostaining clearly identified CD45RO-positive cells as responsible for VEGF/VPF expression in such areas. No correlation could be demonstrated between VEGF/VPF immunostaining and extent of vasa vasorum. These findings thus establish that postnatal VEGF/VPF expression is a feature of normal human arteries and veins and is often extensively expressed in arteries narrowed by atherosclerotic plaque. VEGF/VPF expression in the wall and/or plaque of medium to large vessels suggests a role for VEGF/VPF other than promoting angiogenesis. This role may involve maintenance and repair of luminal endothelium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aorta, Thoracic / chemistry*
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Arteriosclerosis / metabolism*
  • Arteriosclerosis / pathology
  • Endothelial Growth Factors / analysis*
  • Endothelial Growth Factors / biosynthesis
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / metabolism
  • Humans
  • Lymphokines / analysis*
  • Lymphokines / biosynthesis
  • Lymphokines / immunology
  • Lymphokines / metabolism
  • Mammary Arteries / chemistry*
  • Mammary Arteries / metabolism
  • Mammary Arteries / pathology
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptors, Growth Factor / biosynthesis
  • Receptors, Vascular Endothelial Growth Factor
  • Saphenous Vein / chemistry
  • Saphenous Vein / metabolism
  • Saphenous Vein / pathology
  • Staining and Labeling
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor