Dysregulation of cadherins in the intercalated disc of the spontaneously hypertensive stroke-prone rat.
The structural integrity of cardiac cells is maintained by the Ca(2+)-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 18 weeks 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.
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University place, Glasgow, G12 8TA, UK.
Margaret Anne
MA
Craig
Martin W
MW
McBride
Godfrey
G
Smith
Sarah J
SJ
George
Andrew
A
Baker
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D006332:Cardiomegaly / Q000473:pathology; D002448:Cell Adhesion; D005786:Gene Expression Regulation; D006973:Hypertension / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D032383:Myocytes, Cardiac / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000473:pathology*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D051176:beta Catenin