title: Monocytes contribute to the atherosclerotic cap by transformation into fibrocytes.
abstract: OBJECTIVE
  The stability of an atherosclerotic plaque is a key-determining factor in the clinical outcome of cardiovascular disease. In this respect, smooth muscle (SM) alfa actin positive cells play an important role in maintaining plaque stability through formation of a fibrous cap. Recent evidence suggests that circulating progenitors may be a source of these cells. We hypothesized that they may be fibrocytes bone-marrow derived cells that acquire SM-like characteristics, including the expression of SM alfa actin.
  
  
  METHODS
  We examined human carotid endarterectomy specimens for the presence of fibrocytes by immunohistochemistry staining for CD34/procollagen I and leukocyte specific protein-1/procollagen I) and examined fibrocyte differentiation in vitro.
  
  
  RESULTS
  Fibrocytes were found in regions of plaque growth/healing. They possessed a SM-like spindle shape, produced collagen, and consistent with being fibrocytes they co-localized with transformation growth factor beta, but not serum amyloid P factors, known to promote and inhibit their formation, respectively. While fibrocytes were detected in regions of new growth in 35/40 specimens, only 1/3 of the specimens expressed the SM cell marker calponin, and smoothelin was absent, in these regions.
  
  
  CONCLUSIONS
  Our results demonstrate that fibrocytes contribute to formation of the fibrous cap. With fibrocytes being a monocyte derived cell, we suggest that monocytes may play a more crucial role in the clinical outcome of atherosclerosis than previously realized as they not only contribute directly to plaque instability (through foam cell formation), but also promote plaque stability by transformation into a fibrocyte.
authors.affiliation: Vascular Biology Research Centre, Department of Surgery, University of Sydney, Westmead Hospital, Westmead, NSW, Australia. hmedbury@med.usyd.edu.au
authors.forename: H J
authors.initials: HJ
authors.lastname: Medbury
authors.forename: S L S
authors.initials: SL
authors.lastname: Tarran
authors.forename: A K
authors.initials: AK
authors.lastname: Guiffre
authors.forename: M M Y
authors.initials: MM
authors.lastname: Williams
authors.forename: T H
authors.initials: TH
authors.lastname: Lam
authors.forename: M
authors.initials: M
authors.lastname: Vicaretti
authors.forename: J P
authors.initials: JP
authors.lastname: Fletcher
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology*; D016893:Carotid Stenosis / Q000473:pathology; D005487:Foam Cells / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D009000:Monocytes / Q000502:physiology*; D011347:Procollagen / Q000378:metabolism; D012189:Retrospective Studies; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D011347:Procollagen; C067980:CD68 antigen, human; D000097382:CD68 Molecule