title: Decreased caveolin-1 in atheroma: loss of antiproliferative control of vascular smooth muscle cells in atherosclerosis.
abstract: OBJECTIVE
  Proliferation of vascular smooth muscle cells (VSMC) is involved in the pathogenesis of primary atherosclerosis and restenosis after angioplasty. On the background of the antiproliferative activities of caveolin-1, the present study focused on the expression of caveolin-1 in proliferating VSMC of human atheroma.
  
  
  METHODS
  VSMC were isolated from wild-type (Wt) and caveolin-1 knockout mice (Cav-/-). Proliferation of Wt-VSMC after supplementation of serum or Cav-/-VSMC after adenoviral overexpression of caveolin-1 was documented by either Western blot analysis of the cyclin-dependent kinase (Cdk) inhibitor p27kip1 and the proliferating cell nuclear antigen (PCNA) or BrdU incorporation. Using immunohistochemistry the proliferation of VSMC derived from atheroma of human carotid vessels as well as the expression of caveolin-1 in these cells were investigated ex vivo.
  
  
  RESULTS
  Supplementation of serum to Wt-VSMC resulted in an augmented cell cycle entry and a concomitant decrease of caveolin-1 expression. Inversely, adenoviral overexpression of caveolin-1 in Cav-/-VSMC inhibited cellular proliferation. Corresponding to these in vitro data, the expression of caveolin-1 was significantly decreased in proliferating VSMC of human atheroma.
  
  
  CONCLUSIONS
  The proliferation of VSMC in vitro and in human atheroma is associated with a decrease of caveolin-1 expression. These data suggest that the loss of antiproliferative control by caveolin-1 plays a pivotal role in VSMC proliferation in atherosclerosis.
authors.affiliation: Medical Clinic II, Department of Cardiology, University of Technology Dresden, Fetscherstr. 76, 01307, Dresden, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwencke
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmeisser
authors.forename: Christina
authors.initials: C
authors.lastname: Walter
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.forename: Sven
authors.initials: S
authors.lastname: Pannach
authors.forename: Brigitta
authors.initials: B
authors.lastname: Weck
authors.forename: Ruediger C
authors.initials: RC
authors.lastname: Braun-Dullaeus
authors.forename: Michael
authors.initials: M
authors.lastname: Kasper
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
mesh_terms: D000199:Actins / Q000032:analysis; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014161:Transduction, Genetic
chemical_list: D000199:Actins; D051242:Caveolin 1