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.

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.

• Authors: Sadie C Slater, Evgenia Koutsouki, Christopher L Jackson, Raymond C Bush, Gianni D Angelini, Andrew C Newby, Sarah J George
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 7 Pg. 1204-10 (Jul 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 15117735 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Ctnnb1 protein, rat
• Cytoskeletal Proteins
• HAV peptide
• Macromolecular Substances
• Oligopeptides
• R-cadherin
• Trans-Activators
• beta Catenin
• Cyclin D1

Topics

• Animals
• Aorta (injuries, pathology)
• Cadherins (biosynthesis, genetics, physiology)
• Carotid Artery Injuries (pathology)
• Catheterization (adverse effects)
• Cell Division (drug effects)
• Cyclin D1 (biosynthesis, genetics)
• Cytoskeletal Proteins (physiology)
• DNA Replication
• Macromolecular Substances
• Male
• Muscle, Smooth, Vascular (cytology, metabolism)
• Myocytes, Smooth Muscle (cytology, metabolism)
• Oligopeptides (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Trans-Activators (physiology)
• beta Catenin