Vascular endothelial growth factor is associated with histological instability of carotid plaques

Br J Surg. 2008 May;95(5):576-81. doi: 10.1002/bjs.6100.


Background: Vascular endothelial growth factor (VEGF) promotes events favouring carotid plaque instability: inflammatory chemoattraction, thrombogenesis, and upregulation of matrix metalloproteinases and cell adhesion molecules. The aim of this study was to assess neovascularization, VEGF and its receptors in high-grade stable and unstable carotid plaques.

Methods: Immunohistochemical staining for CD34, VEGF, VEGF receptor (VEGFR) 1 and VEGFR2 was performed in 34 intact carotid endarterectomy specimens, and compared in sections demonstrating maximal histological instability (cap rupture/thinning) or, if stable, maximal stenosis.

Results: VEGF staining was increased in 12 unstable compared with 22 stable plaques (median (interquartile range, i.q.r.) plaque score 4.0 (4.0-4.0) versus 3.0 (2.0-3.0); P = 0.002) with upregulation of VEGFR1 (plaque score 4.0 (2.0-4.0) versus 2.0 (1.0-3.0); P = 0.016). In unstable plaques this was associated with increased microvessel density in the cap (median (i.q.r.) 12.1 (4.0-30.0) versus 1.1 (0.0-7.3) microvessels/mm(2); P = 0.017) and shoulder regions (7.7 (3.4-21.4) versus 3.1 (0.4-10.8) microvessels/mm(2); P = 0.176).

Conclusion: Increased VEGF and receptor staining were seen in histologically unstable carotid plaques. Although these differences could reflect cytokine-driven inflammatory events accompanying plaque instability, VEGF and VEGFR1 could be key mediators.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / metabolism
  • Carotid Stenosis / metabolism
  • Carotid Stenosis / pathology*
  • Carotid Stenosis / physiopathology
  • Female
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism
  • Male
  • Microcirculation
  • Middle Aged
  • Neovascularization, Physiologic / physiology
  • Observer Variation
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Vascular Endothelial Growth Factor A / metabolism*


  • Antigens, CD34
  • Vascular Endothelial Growth Factor A
  • Receptors, Vascular Endothelial Growth Factor