on April 29, 2004
Published online before print April 29, 2004, doi: 10.1161/01.ATV.0000130464.24599.e0
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Submitted on March 7, 2004
Accepted on March 23, 2004
R-Cadherin:
-Catenin Complex and Its Association With Vascular Smooth Muscle Cell Proliferation
Sadie C. Slater ;
From Bristol Heart Institute, Department of Cardiac, Anesthetics and Radiological Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, UK.
* To whom correspondence should be addressed. E-mail: s.j.george{at}bris.ac.uk.
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:
-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 -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 -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 -catenin in the nucleus and expressing cyclin D1 in aortic rings.
Conclusions--These results suggest that R-cadherin expression and -catenin signaling may be associated with increased cyclin D1 expression and VSMC proliferation and may therefore play an important role in vascular disease.
Key words: smooth muscle • cadherin • proliferation • intimal thickening
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