Dysregulation of cadherins in the intercalated disc of the spontaneously hypertensive stroke-prone rat

Craig, M. A., McBride, M. W. , Smith, G., George, S. and Baker, A. (2010) Dysregulation of cadherins in the intercalated disc of the spontaneously hypertensive stroke-prone rat. Journal of Molecular and Cellular Cardiology, 48(6), pp. 1121-1128. (doi:10.1016/j.yjmcc.2010.01.017)

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Publisher's URL: http://dx.doi.org/10.1016/j.yjmcc.2010.01.017

Abstract

The structural integrity of cardiac cells is maintained by the Ca2+-dependent homophilic cell-cell adhesion of cadherins. N-cadherin is responsible for this adhesion under normal physiological conditions. The role of cadherins in adverse cardiac pathology is less clear. We studied the hearts of the stroke-prone spontaneously hypertensive (SHRSP) rat as a genetic model of cardiac hypertrophy and compared them to Wistar-Kyoto control animals. Western blotting of protein homogenates from 12-week old SHRSP animals indicated that similar levels of [beta], [gamma]-, and [alpha]-catenin and T, N and R-cadherin were expressed in the control and SHRSP animals. However, dramatically higher levels of E-cadherin were detected in SHRSP animals compared to controls at 6, 12 and 18áweeks of age. This was confirmed by quantitative Taqman PCR and immunohistochemistry. E-cadherin was located at the intercalated disc of the myocytes in co-localisation with connexin 43. Adenoviral overexpression of E-cadherin in rat H9c2 cells and primary rabbit myocytes resulted in a significant reduction in myocyte cell diameter and breadth. E-cadherin overexpression resulted in re-localisation of [beta]-catenin to the cell surface particularly to cell-cell junctions. Subsequent immunohistochemistry of the hearts of WKY and SHRSP animals also revealed increased levels of [beta]-catenin in the intercalated disc in the SHRSP compared to WKY. Therefore, remodelling of the intercalated disc in the hearts of SHRSP animals may contribute to the altered function observed in these animals

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:George, Dr Sarah and Smith, Professor Godfrey and Baker, Professor Andrew and McBride, Dr Martin and Craig, Dr Margaret
Authors: Craig, M. A., McBride, M. W., Smith, G., George, S., and Baker, A.
Subjects:Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Molecular and Cellular Cardiology
Publisher:Elsevier
ISSN:0022-2828
ISSN (Online):1095-8584
Published Online:06 February 2010
Copyright Holders:Copyright © 2010 Elsevier Ltd.
First Published:First published in Journal of Molecular and Cellular Cardiology 48(6):1121-1128
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
404721Unravelling the effect of cadherin dysregulation in the heartAndrew BakerWellcome Trust (WELLCOME)078399/Z/05/ZInstitute of Cardiovascular and Medical Sciences