CLINICAL/MOLECULAR FEATURES AND PROTEOMICS DATA TO IDENTIFY DETERMINANTS OF CAROTID PLAQUE RISK

Carotid plaque stenosis is responsible of 15-20% of all ischemic strokes; despite that, asymptomatic stenosis represents a therapeutic dilemma. The best medical treatment (BMT) alone, instead of surgery, may be adequate to prevent the risk of ictus in the majority of patients with carotid stenosis that will never encounter ischemic complications. Currently the surgical indication of asymptomatic plaque is only based on the stenosis degree measured by imaging methods. Identification of vulnerability markers of carotid plaques could help to select patients who really will take advantage from carotid endarterectomy. In literature many factors are under investigation for identifying plaques with a major risk of stroke; among these plaque morphology, intracerebral circulation assessment, silent stroke identification and biomarkers are proposed as possible decision making tools. Regarding biomarkers, several proteomics approaches have been up to now used to elucidate the molecular mechanisms involved in plaque formation and complication. In particular the analysis of plaque secretome (proteins secreted by the plaque) in patients submitted to carotid endarterectomy could bring more informations compared to proteome, because secretome mimics the in vivo condition and presents a reduced complexity, allowing the detection of under-represented potential biomarkers. The aim of this thesis is: at first, to review the literature concerning the identification of all vulnerability factors in patients with asymptomatic carotid stenosis, and subsequently to characterize the plaque secretome in patients submitted to carotid endarterectomy.