Introduction Stroke is the third most common cause of death world wide. Most cases of stroke are caused by atherosclerotic plaque rupture. A challenge facing clinicians is identifying asymptomatic patients at risk of plaque instability. Locally released angiogenic growth factors may contribute to microvessel instability within plaques. Growth factors and inflammatory cytokines are potential serum biomarkers to identify patients at risk of stroke.
Materials and methods Immunohistochemistry and quantitative PCR (Q-PCR) were used to establish localisation and expression of angiogenic growth factors within carotid endarterectomy specimens from symptomatic and asymptomatic patients. Stable or unstable microvessels were distinguished by CD31 and CD105 staining. Systemic levels of circulating angiogenic growth factors and inflammatory cytokines were measured in venous blood using Bio-Plex arrays.
Results Hepatocyte growth factor (HGF) and its receptor c-Met were detected in CD31-positive endothelia, and α-SMA-positive cells, respectively. Q-PCR demonstrated upregulation of the angiogenic factors CD105, HGF (p<0.001) and c-Met (p=0.011) in symptomatic versus asymptomatic plaques. A significantly greater neovessel density was detected in symptomatic plaques (p=0.042), associated with elevated expression of HGF and c-Met. Suspension arrays demonstrated elevated HGF (p=0.002) and decreased platelet-derived growth factor (PDGF; p=0.036) serum levels in symptomatic versus asymptomatic patients. Twenty-seven cytokines were examined; seven endarterectomy patients demonstrated significantly increased levels in comparison with controls. No differences were observed between preoperative and postoperative serum.
Discussion Plaque instability may be mediated by HGF-induced formation of microvessels, and decreased PDGF. We will investigate the effects of inflammatory cytokines with a view to comparing symptomatic versus asymptomatic patients. Targeting surgery to those who will benefit would eliminate unnecessary risk.
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