Inhibition of N-cadherin retards smooth muscle cell migration and intimal thickening via induction of apoptosis.

Journal of Vascular Surgery
Cressida A LyonSarah Jane George

Abstract

Inhibition of vascular smooth muscle cell (VSMC) migration is a potential strategy for reducing intimal thickening during in-stent restenosis and vein graft failure. In this study, we examined the effect of disrupting the function of the VSMC adhesion molecule, N-cadherin, using antagonists, neutralizing antibodies, and a dominant negative, on VSMC migration and intimal thickening. Migration was assessed by the scratch-wound assay of human saphenous vein VSMCs and in a human saphenous vein ex vivo organ culture model of intimal thickening. Inhibition of cadherin function using a pan-cadherin antagonist, significantly reduced migration by 53%±8% compared with the control peptide (n=3; P<.05). Furthermore, inhibition of N-cadherin function with an N-cadherin antagonist, neutralizing antibodies, and adenoviral expression of dominant negative N-cadherin (RAd dn-N-cadherin), significantly reduced migration by 31%±2%, 23%±1% and 32%±7% compared with controls, respectively (n=3; P<.05). Inhibition of cadherin function significantly increased apoptosis by between 1.5- and 3.3-fold at the wound edge. In an ex vivo model of intimal thickening, inhibition of N-cadherin function by infection of human saphenous vein segments with RAd dn-N-c...Continue Reading

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Citations

Nov 22, 2011·Cardiovascular Research·Dammanahalli K JagadeeshaFrancis J Miller
Mar 8, 2011·Biological Chemistry·Johannes M NuessleAndre Menke
Apr 23, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yong Guang XiaoZhi Fu Mao
Jan 28, 2012·Cell and Tissue Research·Orest W Blaschuk
Nov 21, 2015·Vascular Pharmacology·Cressida A LyonSarah J George
Aug 16, 2011·Journal of the American College of Surgeons·Shunsuke YoshidaFrank W LoGerfo
Aug 19, 2015·Journal of Biomechanics·Kerianne E SteuckePatrick W Alford
Jul 22, 2015·British Journal of Haematology·Krzysztof M MrozikKate Vandyke
Apr 9, 2016·Cells·Jing Ling HoonCheng-Gee Koh
Aug 6, 2013·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Raquel Carvalho MontenegroManoel Odorico de Moraes
Apr 20, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Monika K GrudzinskaPiotr Religa
May 13, 2018·Bioscience Reports·Xueqin WangXiangyu Zhou
Jun 30, 2019·Journal of Muscle Research and Cell Motility·TecLino AfewerkiDerek Warren
Feb 8, 2018·Cellular Signalling·Agne FrismantieneTherese J Resink

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Methods Mentioned

BETA
coronary artery bypass
FCS

Software Mentioned

Media Cybernetics Image Pro Plus

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