Copyright © 2005, European Society of Cardiology
Decreased caveolin-1 in atheroma: Loss of antiproliferative control of vascular smooth muscle cells in atherosclerosis
aMedical Clinic II, Department of Cardiology, University of Technology Dresden, Fetscherstr. 76, 01307, Dresden, Germany
bDepartment of Anatomy, University of Technology Dresden, Dresden, Germany
* Corresponding author. Tel.: +49 351 4501704; fax: +49 351 4501702. Email address: Ruth.Strasser{at}mailbox.tu-dresden.de
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.
Conclusion: 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.
KEYWORDS Atherosclerosis; Caveolae; Signal transduction; Smooth muscle
1 C. Schwencke and A. Schmeisser contributed equally to this work.
Time for primary review 22 days
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