The mechanism(s) mediating atherosclerotic calcification may be similar to those governing bone remodeling, and osteoblast-like cells have been observed in plaque. We tested the hypothesis that osteoclast-like cells (OLCs) also exist in atherosclerotic arteries. In 205 tissue blocks obtained from 21 patients undergoing
carotid endarterectomy, we performed histopathologic analysis, histochemical staining for
tartrate-resistant acid phosphatase (TRAP), and immunohistochemical analysis for osteoclast and macrophage
antigens, including CD68, colony stimulating factor-1 receptor (CSF-1R),
cathepsin K (cat-K), receptor activator of nuclear factor-κB (RANK), and
osteoprotegerin (OPG). Lesions were classified according to the AHA system, and further grouped as calcified or non-calcified (with necrotic cores or
suture granulomas). Multinucleated giant cells morphologically similar to osteoclasts were frequently seen, sometimes exhibited morphologic evidence of polarization, were closely associated with regions of calcification,
fibrosis, or granulomatous tissue, and also appeared to be associated with neovascularization and regions of intraplaque
hemorrhage. TRAP-positive cells often expressed the osteoclast-associated
antigens cat-K, RANK, and OPG. Calcification typically occurred at the base of plaque or in necrotic cores in various morphologies, including a fine powdery pattern, a diffuse pattern of larger deposits near
cholesterol clefts and necrotic centers, and nodular forms. Regions of frank ossification were rarely observed.
CONCLUSION: OLCs are frequently found in plaque, and co-localize with sub-regions of
cholesterol deposition, mineralization, and necrotic and foreign debris. True bone tissue is rare in carotid plaque, although more common in other arteries. Our findings suggest that arterial OLCs might degrade
mineral deposits, prevent formation of calcification or both and therefore counterbalance the activity of the osteoblast-like cells in
atherosclerosis.