(Circulation. 1997;96:3360-3368.)
© 1997 American Heart Association, Inc.
Articles |
Topographic Analysis of Proliferative Activity in Carotid Endarterectomy Specimens by Immunocytochemical Detection of the Cell Cycle–Related Antigen Ki-67
From the Department of Vascular Surgery (R.B., K.H., P.C.M.), the Institute for Pathology and Pathological Anatomy (T.R., W.N.), and the Institute for Medical Statistics and Epidemiology (M.G.W.), Rechts der Isar Medical School, Technical University of Munich (Germany).
Correspondence to Richard Brandl, MD, Department of Vascular Surgery, Technical University of Munich Medical School, Rechts der Isar Medical Center, Ismaninger Str. 22, 81675 Munich, Germany.
Background On the basis of contradictory results found in animal experiments and coronary atherectomy tissue, there is an ongoing debate about 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 distinct regions of human carotid endarterectomy specimens harvested en bloc by surgical biopsy.
Methods and Results After en bloc resection, serial sections of
26 consecutive carotid lesions were analyzed by
histomorphological examination and immunohistochemistry. Thereby, 319
high-power fields were attributed to separate plaque regions defined as
follows: distal boundary of the lesion with normal intima, plaque
shoulder, core region, and diffuse intimal thickening.
Endothelial cells, smooth muscle cells, T cells, and
macrophages were identified by immunostaining
of factor VIII–related protein, 
-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 characterized by high cell density (>1000 cells/mm2)
as well as in reparative sites in the perimeter of
atheroma, intramural thrombosis, plaque hemorrhage,
and neovascularization (P<.01). Few or no signs of proliferation
activity were found in normal intima, in areas of dense -actin
positivity, or adjacent media. As shown by double
immunostaining, macrophages and unspecified
mesenchymal cells represented the prevailing proliferating
cell type.
Conclusions Our results suggest that proliferation in advanced
human carotid lesions is confined to the intima and focally
concentrated in central plaque regions negative for -actin.
Furthermore, it apparently occurs primarily as part of inflammatory
processes and structural repair predominantly involving
macrophages, as well as unspecific mesenchymal cells.
Key Words: arteriosclerosis • carotid arteries • cells • immunohistochemistry • muscle, smooth • plaque
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