TOPOGRAPHIC ANALYSIS OF PROLIFERATIVE ACTIVITY IN CAROTID ENDARTERECTOMY SPECIMENS BY IMMUNOCYTOCHEMICAL DETECTION OF THE CELL CYCLE-RELATED ANTIGEN KI-67

Background On the basis of contradictory results found in animal exper iments and coronary atherectomy tissue, there is an ongoing debate abo ut the significance of cellular proliferation in human atherosclerosis . In the present prospective study, the cell cycle-related antigen Ki- 67 was detected for topographic determination of cell turnover in dist inct regions of human carotid endarterectomy specimens harvested en bl oc by surgical biopsy. Methods and Results After en bloc resection, se rial sections of 26 consecutive carotid lesions were analyzed by histo morphological examination and immunohistochemistry. Thereby, 319 high- power fields were attributed to separate plaque regions defined as fol lows: distal boundary of the lesion with normal intima, plaque shoulde r, core region, and diffuse intimal thickening. Endothelial cells, smo oth muscle cells, T cells, and macrophages were identified by immunost aining of factor VIII-related protein, alpha-actin, CD68, and CD45R0. An overall proliferation index of 0.49+/-1.05% was yielded by positive anti-Ki-67 immunolabeling, predominantly in macrophage-rich areas cha racterized by high cell density (>1000 cells/mm(2)) as well as in repa rative sites in the perimeter of atheroma, intramural thrombosis, plaq ue hemorrhage, and neovascularization (P<.01). Few or no signs of prol iferation activity were found in normal intima, in areas of dense alph a-actin positivity, or adjacent media. As shown by double immunostaini ng, macrophages and unspecified mesenchymal cells represented the prev ailing proliferating cell type. Conclusions Our results suggest that p roliferation in advanced human carotid lesions is confined to the inti ma and focally concentrated in central plaque regions negative far alp ha-actin. Furthermore, it apparently occurs primarily as part of infla mmatory processes and structural repair predominantly involving macrop hages, as well as unspecific mesenchymal cells.