Decreased caveolin-1 in atheroma: loss of antiproliferative control of vascular smooth muscle cells in atherosclerosis.
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.
Schwencke
Carsten
C
Medical Clinic II, Department of Cardiology, University of Technology Dresden, Fetscherstr. 76, 01307, Dresden, Germany.
Schmeisser
Alexander
A
Walter
Christina
C
Wachter
Rolf
R
Pannach
Sven
S
Weck
Brigitta
B
Braun-Dullaeus
Ruediger C
RC
Kasper
Michael
M
Strasser
Ruth H
RH
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
D000199:Actins; D051242:Caveolin 1