Background. Although smooth muscle cell proliferation is a prominent f
eature of restenosis in experimental models, the role of cellular prol
iferation in the initiation and progression of carotid restenosis is n
ot well documented. Methods. Between 1985 and 1995, 35 carotid endarte
rectomies (CEA) in 34 patients were performed for restenosis. Patient
risk factors, cerebrovascular symptoms, and operative findings were re
corded. Tissue specimens from 29 of these cases and 14 original specim
ens from the same patient were examined by light microscopy (H&E, tric
hrome, elastochrome, and Alcian blue) and immunohistochemistry (alpha
actin, CD 68, vWF, and proliferating nuclear cell antigen (PCNA)) in o
rder to determine the morphologic characteristics and cellular prolife
rative activity of the plaque. Results. Hemodynamically significant re
current stenosis occurred in the 29 patients (69% symptomatic) between
2 months and 30 years after their initial CEAs, Eleven of 29 (38%) le
sions were removed early (<3 years). Recurrent lesions were characteri
zed based on their components as neointimal thickening, 24% (7/29), ne
ointimal thickening and atherosclerosis, 55% (16/29), or atherosclerot
ic, 21% (6/29), Nineteen of 29 (66%) plaques were complicated by mural
thrombus or intraplaque hemorrhage. An inflammatory cell infiltrate c
onsisting of macrophages and T lymphocytes was observed adjacent to ar
eas of recurrent atherosclerosis and macrophages in regions of intimal
thickening. Although infrequently present (generally 1-3% of cells) P
CNA-positive cells were detected in 41% (12 of 29) of recurrent and 14
% (2 of 14) of primary plaques. No PCNA-positive cells were detected i
n the remaining 67% (29 of 43) of specimens. There was no statistical
difference in the number of PCNA-positive cells in early recurrent les
ions compared to those recurring after 3 years (36% vs 44%). PCNA immu
noreactivity when present was most commonly noted in macrophages assoc
iated with thrombus or atheroma rather than smooth muscle cells. Concl
usions. Although evidence of cellular proliferation was observed in 40
% of recurrent carotid endarterectomy lesions, the proliferation rate
was low (1-3%) and unrelated to the time interval of recurrence. Proli
ferative activity was most pronounced in macrophages associated with i
ntraplaque hemorrhage or atheroma, The contribution of inflammatory ce
lls to the biologic behavior of restenotic lesions requires further in
vestigation. (C) 1998 Academic Press.