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.


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.
Slater
Sadie C
SC
Bristol Heart Institute, Department of Cardiac, Anesthetic, and Radiological Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, UK.
Koutsouki
Evgenia
E
Jackson
Christopher L
CL
Bush
Raymond C
RC
Angelini
Gianni D
GD
Newby
Andrew C
AC
George
Sarah J
SJ
D000818:Animals; D001011:Aorta / Q000293:injuries / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020212:Carotid Artery Injuries / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004261:DNA Replication; D046911:Macromolecular Substances; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D051176:beta Catenin
D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; C495232:HAV peptide; D046911:Macromolecular Substances; D009842:Oligopeptides; C083970:R-cadherin; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1