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


CONCLUSIONS
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.
Russell
D A
DA
Department of Vascular Surgery, The General Infirmary at Leeds, Leeds, UK. davearussell@aol.com
Abbott
C R
CR
Gough
M J
MJ
D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D015588:Observer Variation; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor