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.
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 humanatheroma. 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 humanatheroma. CONCLUSION: The proliferation of VSMC in vitro and in humanatheroma 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: David Engel; Linda Beckers; Erwin Wijnands; Tom Seijkens; Dirk Lievens; Maik Drechsler; Norbert Gerdes; Oliver Soehnlein; Mat J A P Daemen; Radu V Stan; Erik A L Biessen; Esther Lutgens Journal: FASEB J Date: 2011-07-27 Impact factor: 5.191
Authors: Carlos Fernández-Hernando; Jun Yu; Yajaira Suárez; Christoph Rahner; Alberto Dávalos; Miguel A Lasunción; William C Sessa Journal: Cell Metab Date: 2009-07 Impact factor: 27.287
Authors: Juan A Rodriguez-Feo; Willem E Hellings; Frans L Moll; Jean-Paul P M De Vries; Ben J van Middelaar; Ale Algra; Joost Sluijter; Evelyn Velema; Theo van den Broek; William C Sessa; Dominique P V De Kleijn; Gerard Pasterkamp Journal: PLoS One Date: 2008-07-02 Impact factor: 3.240