title: R-cadherin:beta-catenin complex and its association with vascular smooth muscle cell proliferation.
abstract: 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.
authors.affiliation: Bristol Heart Institute, Department of Cardiac, Anesthetic, and Radiological Sciences, University of Bristol, Bristol Royal Infirmary, Bristol, UK.
authors.forename: Sadie C
authors.initials: SC
authors.lastname: Slater
authors.forename: Evgenia
authors.initials: E
authors.lastname: Koutsouki
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Jackson
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Bush
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Newby
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: George
mesh_terms: 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
chemical_list: 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