| Abstract
| - Neointima formation is a process characterized by smooth muscle cell (SMC) proliferationand extracellular matrix deposition in the vascular intimal layer. Here, we critically evaluate the role ofcaveolin-1 (Cav-1) in the pathogenesis of neointima formation. Cav-1 and caveolae organelles areparticularly abundant in SMCs, where they are thought to function in membrane trafficking and signaltransduction events. To directly evaluate the role of Cav-1 in the pathogenesis of neointimal lesions, weused Cav-1-deficient (Cav-1 −/−) mice as a model system. The right common carotid artery of wild-typeand Cav-1 −/− mice was ligated just proximal to its bifurcation. Specimens were then harvested 4-weekspostligation and processed for morphometric and immunohistochemical analyses. The carotids of Cav-1−/− mice showed significantly more intimal hyperplasia with subtotal luminal obstruction, as comparedto wild-type mice. These neointimal lesions consisted mainly of SMCs. Mechanistically, neointimal lesionsderived from Cav-1 −/− mice exhibited higher levels of phospho-p42/44 MAP kinase and cyclin D1immunostaining, consistent with the idea that Cav-1 functions as a negative regulator of signal transduction.A significant increase in phospho-Rb (Ser780) immunostaining was also observed, in line with theupregulation of cyclin D1. In conclusion, using a carotid artery blood-flow cessation model, we showthat genetic ablation of Cav-1 in mice stimulates SMC proliferation (neointimal hyperplasia), withconcomitant activation of the p42/44 MAP kinase cascade and upregulation of cyclin D1. Importantly,our current study is the first to investigate the role of Cav-1 in SMC proliferation in the vascular systemusing Cav-1 −/− mice.
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