A Comparative Study of Carotid Atherosclerotic Plaque Microvessel Density and Angiogenic Growth Factor Expression in Symptomatic Versus Asymptomatic Patients

ObjectiveA 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.MethodsCarotid 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.ResultsImmunofluorescence 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.ConclusionPlaque 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.