A comparative study of carotid atherosclerotic plaque microvessel density and angiogenic growth factor expression in symptomatic versus asymptomatic patients.
OBJECTIVE
A challenge facing clinicians is identifying patients with asymptomatic carotid disease at risk of plaque instability. We hypothesise that locally released angiogenic growth factors contribute to plaque instability.


METHODS
Carotid endarterectomy specimens from eight symptomatic and eight asymptomatic patients were interrogated for microvessel density and angiogenic growth factor expression histologically using immunofluorescence, and biochemically using quantitative real-time polymerase chain reaction (q-RT-PCR). Bio-Plex suspension array was used to assess circulating biomarkers in venous blood from the same patients and six healthy age-matched controls.


RESULTS
Immunofluorescence demonstrated significantly greater neovessel density in symptomatic plaques (P=0.010) with elevated expression of hepatocyte growth factor (HGF) (P=0.001) and its receptor MET (P=0.011) than in asymptomatic plaques. The q-RT-PCR demonstrated up-regulation of Endoglin (CD105), HGF (P=0.001) and MET (P=0.011) in the plaques of symptomatic versus asymptomatic patients. Bio-Plex suspension array demonstrated elevated HGF (P=0.002) serum levels in symptomatic versus asymptomatic patients and healthy controls, and decreased platelet-derived growth factor (PDGF) (P=0.036) serum levels in symptomatic versus asymptomatic patients.


CONCLUSIONS
Plaque instability may be mediated by HGF-induced formation of new microvessels, and decreased vessel stability resulting from decreased PDGF. Suspension array technology has the potential to identify circulating biomarkers that correlate with plaque rupture risk.
Chowdhury
M
M
Department of Vascular & Endovascular Surgery, Manchester Royal Infirmary, Manchester, UK. mo.chowdhury@doctors.org.uk
Ghosh
J
J
Slevin
M
M
Smyth
J V
JV
Alexander
M Y
MY
Serracino-Inglott
F
F
D000199:Actins / Q000032:analysis; D000368:Aged; D042501:Angiogenic Proteins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D002343:Carotid Artery, Internal / Q000737:chemistry* / Q000473:pathology*; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D018450:Disease Progression; D016894:Endarterectomy, Carotid; D000071063:Endoglin; D005260:Female; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000032:analysis; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D018570:Risk Assessment; D012421:Rupture; D020521:Stroke / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
D000199:Actins; D042501:Angiogenic Proteins; D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; C066855:HGF protein, human; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met