TY - JOUR
T1 - Defective Intercellular Adhesion Complex in Myocardium Predisposes to Infarct Rupture in Humans
AU - van den Borne, Susanne W.M.
AU - Narula, Jagat
AU - Voncken, J. Willem
AU - Lijnen, Peter M.
AU - Vervoort-Peters, Helena T.M.
AU - Dahlmans, Vivian E.H.
AU - Smits, Jos F.M.
AU - Daemen, Mat J.A.P.
AU - Blankesteijn, W. Matthijs
N1 - Funding Information:
This study was supported by Maastricht University. William C. Roberts, MD, served as Guest Editor for this article.
PY - 2008/6/3
Y1 - 2008/6/3
N2 - Objectives: Our goal was to evaluate intercellular adhesion complex proteins in myocardium in human infarct rupture. Background: Infarct rupture, a fatal complication of myocardial infarction (MI), has been attributed to a defective cell adhesion complex in a transgenic mouse model. Methods: Heart samples were collected from autopsies from infarct rupture and control (nonrupture) MI patients. Both infarcted and remote areas were included. Cell adhesion proteins including αE-catenin, β-catenin, γ-catenin, and N-cadherin were characterized by immunohistochemistry and immunoblotting. Genetic analysis was undertaken to evaluate mutations and polymorphisms in the αE-catenin gene. In addition, infarct rupture was studied in transgenic mice heterozygous for αE-catenin C-terminal deficiency, mimicking the situation in human infarct rupture patients. Results: No αE-catenin was detected in 70% of remote samples of infarct rupture hearts compared with 20% in control MI by immunohistochemistry. The immunoblot analysis confirmed a significant reduction in remote areas, and complete absence of αE-catenin in infarct areas from infarct rupture patients. No mutation or polymorphism of the αE-catenin gene was discovered. Other cell adhesion proteins were not significantly affected in remote areas of infarct rupture hearts. Three-fourths of the heterozygous αE-catenin C-terminal truncated mice died of infarct rupture, compared with one-fourth of the wild-type littermates. Conclusions: The data show a reduced expression and defective localization of αE-catenin in the intercalated disc region in patients dying of infarct rupture. The mechanism of lower expression of αE-catenin remains to be elucidated.
AB - Objectives: Our goal was to evaluate intercellular adhesion complex proteins in myocardium in human infarct rupture. Background: Infarct rupture, a fatal complication of myocardial infarction (MI), has been attributed to a defective cell adhesion complex in a transgenic mouse model. Methods: Heart samples were collected from autopsies from infarct rupture and control (nonrupture) MI patients. Both infarcted and remote areas were included. Cell adhesion proteins including αE-catenin, β-catenin, γ-catenin, and N-cadherin were characterized by immunohistochemistry and immunoblotting. Genetic analysis was undertaken to evaluate mutations and polymorphisms in the αE-catenin gene. In addition, infarct rupture was studied in transgenic mice heterozygous for αE-catenin C-terminal deficiency, mimicking the situation in human infarct rupture patients. Results: No αE-catenin was detected in 70% of remote samples of infarct rupture hearts compared with 20% in control MI by immunohistochemistry. The immunoblot analysis confirmed a significant reduction in remote areas, and complete absence of αE-catenin in infarct areas from infarct rupture patients. No mutation or polymorphism of the αE-catenin gene was discovered. Other cell adhesion proteins were not significantly affected in remote areas of infarct rupture hearts. Three-fourths of the heterozygous αE-catenin C-terminal truncated mice died of infarct rupture, compared with one-fourth of the wild-type littermates. Conclusions: The data show a reduced expression and defective localization of αE-catenin in the intercalated disc region in patients dying of infarct rupture. The mechanism of lower expression of αE-catenin remains to be elucidated.
UR - http://www.scopus.com/inward/record.url?scp=44049084003&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2008.02.056
DO - 10.1016/j.jacc.2008.02.056
M3 - Article
C2 - 18510968
AN - SCOPUS:44049084003
SN - 0735-1097
VL - 51
SP - 2184
EP - 2192
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 22
ER -