Defective Intercellular Adhesion Complex in Myocardium Predisposes to Infarct Rupture in Humans

Susanne W.M. van den Borne, Jagat Narula, J. Willem Voncken, Peter M. Lijnen, Helena T.M. Vervoort-Peters, Vivian E.H. Dahlmans, Jos F.M. Smits, Mat J.A.P. Daemen, W. Matthijs Blankesteijn

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish
Pages (from-to)2184-2192
Number of pages9
JournalJournal of the American College of Cardiology
Issue number22
StatePublished - 3 Jun 2008
Externally publishedYes


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