Pathobiologic Determinants of Carotid Plaque Development
Carotid plaques play a major role in cerebrovascular diseases (ischemic stroke and transient ischemic attacks (TIA)) that result, in the majority of cases, from embolization of an atherosclerotic plaque or from acute occlusion of the carotid artery with thrombus propagation distally. The clinical settings of carotid artery disease include two major categories: transient ischemic events and ischemic strokes. There are many risk factors for ischemic stroke, while transient ischemic events in patients with significant carotid stenosis are powerful predictors of subsequent stroke. These data suggest two types of carotid artery disease: one form with stable plaque (unlikely to produce symptomatic embolization or carotid occlusion) and a second form, not necessarily more stenotic, sustained from unstable plaque at ‘high risk’ of symptomatic embolization or carotid occlusion. Detailed histological examinations have demonstrated that there are differences in the characteristics of the atherosclerotic plaque removed from symptomatic and asymptomatic patients. In symptomatic patients the necrotic core is located nearer to the fibrous cap, the minimum cap thickness is less, and the inflammatory component is significantly different. Thus, while the degree of carotid stenosis, volume of the fibrous cap, and lipid core may be similar in symptomatic and asymptomatic plaques, the position of the core, local thinning of the cap, and
inflammation may predispose to rupture. Reasons for the difference in plaque evolution may be found in the particular microenvironment that characterizes each plaque, and which results from the balance between cell influx and cell growth and extracellular matrix production and degradation. Moreover, determination of the plaque microenvironment has strong genetic influences, since various genes may contribute singly or in combination to the development of atherosclerosis.