R-cadherin:beta-catenin complex and its association with vascular smooth muscle cell proliferation.
OBJECTIVE: Vascular smooth muscle cell (VSMC) proliferation is an important component of atherosclerosis, restenosis after angioplasty and stent placement, and vein graft failure. Outside-in signaling from the cadherin:beta-catenin complex can increase transcription of the cell-cycle gene cyclin D1; however, its role in VSMC proliferation has only recently been considered. METHODS AND RESULTS: We examined the involvement of R-cadherin and beta-catenin in VSMC proliferation in balloon-injured carotid arteries in vivo and aortic rings in vitro. The number of medial VSMCs positive for R-cadherin was significantly reduced by 32%+/-5%, 52%+/-10%, and 23%+/-2% at 0.25, 24, and 48 hours after injury in vivo, respectively. These changes in cadherin expression coincided with the detection of nuclear beta-catenin and elevated cyclin D1 expression. Furthermore, loss of R-cadherin expression was associated with medial VSMC proliferation. Inhibition of classical cadherin function with a HAV peptide and R-cadherin neutralizing antibodies significantly increased proliferation by 4.3+/-1.0-fold and 4.1+/-0.98-fold, and increased the number of cells with beta-catenin in the nucleus and expressing cyclin D1 in aortic rings. CONCLUSIONS: These results suggest that R-cadherin expression and beta-catenin signaling may be associated with increased cyclin D1 expression and VSMC proliferation and may therefore play an important role in vascular disease.[1]References
- R-cadherin:beta-catenin complex and its association with vascular smooth muscle cell proliferation. Slater, S.C., Koutsouki, E., Jackson, C.L., Bush, R.C., Angelini, G.D., Newby, A.C., George, S.J. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
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