Assessing carotid plaque structure

Sammanfattning: Atherosclerosis is the leading cause of death and disability in the western world. Its clinical complications include acute myocardial infarction, sudden death and stroke. Thirty to 40 % of all ischemic strokes are caused by a carotid stenosis. The acute clinical event is triggered by an occluding thrombosis and even more frequently by embolization. Besides the degree of stenosis, the structure of the carotid plaque can be relevant for the appearance of symptoms. This thesis is focused on different aspects of the human carotid plaque. We compared the biochemical components of plaques from symptomatic and and asymptomatic patients. Plaques from symptomatic patients were less calcified and had more elastin, cholesteryl esters and cells. No differences were found for collagen and sulphated glycosaminoglycans. We also compared the composition of the plaque according to their different characteristics when assessed with standardized high-definition ultrasonography. Echolucent plaques have previously been associated with increased risk for neurological events. We observed that echolucent plaques had less calcium, more elastin and more cells. Surprisingly, in contrast to previous histological reports, our biochemical analysis did not show significant differences in the amounts of lipids or collagen. We also separated different types of elastin present in the plaques and found that intermediate-sized forms were increased both in echolucent and in plaques associated with symptoms. We demonstrated the presence of the transcription factor activator protein-1 (AP-1) and its subunits in human carotid plaques and showed that its activity is increased in symptomatic plaques. AP-1 activity correlated with cholesteryl esters and with elastin. This transcription factor may be involved in lipid accumulation, inflammation and/or tissue remodelling. Finally, we showed that antibodies against specific antigens present in oxidized LDL reflect plaque structure as assessed by histology and immunohistochemistry. IgG against an aldehyde modified apoB-100 fragment (amino acids 3136-3155) was associated with small, lipid-rich and fibrous-poor plaques, whereas IgM against that peptide sequence and against a fragment containing amino acids 3661-3680 were associated with fibrous-rich, lipid-poor plaques with few macrophages. This suggests that monitoring humoral immune response against oxidized-LDL epitopes may be used to identify patients with vulnerable plaques. These studies contribute to a better characterization of the vulnerable carotid plaque, revealing possible new paths for diagnostic and therapeutic strategies.