title: Multinucleated giant cells in atherosclerotic plaques of human carotid arteries: Identification of osteoclast-like cells and their specific proteins in artery wall.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: California Hospital Medical Center, Los Angeles, CA 90015, United States.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Qiao
authors.affiliation: Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mishra
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90048, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, David Geffen School of Medicine at UCLA, Los Angeles, CA 90059, United States.
authors.forename: Satyesh K
authors.initials: SK
authors.lastname: Sinha
authors.affiliation: Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90048, United States; Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, David Geffen School of Medicine at UCLA, Los Angeles, CA 90059, United States. Electronic address: rajavashisth@gmail.com.
authors.forename: Tripathi B
authors.initials: TB
authors.lastname: Rajavashisth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000473:pathology*; D005260:Female; D015726:Giant Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000473:pathology*
chemical_list: D008562:Membrane Glycoproteins
keywords: Calcium; Mineral resorption; Osteoblast; Osteoclast; Plaque