Factor VII Activating Protease Expression in Human Platelets and Accumulation in Symptomatic Carotid Plaque

Background Factor VII activating protease (FSAP) is of interest as a marker for vascular inflammation and plaque destabilization. The aim of this study was to analyze the expression profile of FSAP in endarterectomy specimens that were taken from patients with asymptomatic and symptomatic carotid atherosclerotic plaques and to compare them with circulating FSAP levels. Methods and Results Plasma FSAP concentration, activity, and mRNA expression were measured in endarterectomy specimens and in monocytes and platelets. Plaque and plasma FSAP levels were higher in symptomatic patients (n=10) than in asymptomatic patients (n=14). Stronger FSAP immunostaining was observed in advanced symptomatic lesions, in intraplaque hemorrhage-related structures, and in lipid-rich areas within the necrotic core. FSAP was also colocalized with monocytes and macrophages (CD11b/CD68-positive cells) and platelets (CD41-positive cells) of the plaques. Moreover, human platelets expressed FSAP in vitro, at both the mRNA and protein levels. Expression is stimulated by thrombin receptor-activating peptide and ADP and reduced by acetylsalicylic acid. Conclusions Plasma FSAP levels were significantly increased in patients with symptomatic carotid stenosis and thus may be involved in plaque development This plaque-associated FSAP may be produced by platelets or macrophages or may be taken up from the circulation. To establish FSAP's utility as a circulating or plaque biomarker in patients with symptomatic carotid atherosclerotic plaques, further studies are needed.

Keywords: FSAP; asymptomatic carotid stenosis; atherosclerosis; inflammation; platelet; symptomatic carotid stenosis.