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:β-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 β-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 β-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 β-catenin in the nucleus and expressing cyclin D1 in aortic rings.Conclusions—
These results suggest that R-cadherin expression and β-catenin signaling may be associated with increased cyclin D1 expression and VSMC proliferation and may therefore play an important role in vascular disease.