Defective intercellular adhesion complex in myocardium predisposes to infarct rupture in humans.

Abstract

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 alphaE-catenin, beta-catenin, gamma-catenin, and N-cadherin were characterized by immunohistochemistry and immunoblotting. Genetic analysis was undertaken to evaluate mutations and polymorphisms in the alphaE-catenin gene. In addition, infarct rupture was studied in transgenic mice heterozygous for alphaE-catenin C-terminal deficiency, mimicking the situation in human infarct rupture patients.

RESULTS:

No alphaE-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 alphaE-catenin in infarct areas from infarct rupture patients. No mutation or polymorphism of the alphaE-catenin gene was discovered. Other cell adhesion proteins were not significantly affected in remote areas of infarct rupture hearts. Three-fourths of the heterozygous alphaE-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 alphaE-catenin in the intercalated disc region in patients dying of infarct rupture. The mechanism of lower expression of alphaE-catenin remains to be elucidated.

• Authors: 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
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 51 Issue 22 Pg. 2184-92 (Jun 03 2008) ISSN: 1558-3597 [Electronic] United States
• PMID: 18510968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• Catenins
• Intercellular Adhesion Molecule-1

Topics

• Aged
• Aged, 80 and over
• Animals
• Cadaver
• Cadherins (metabolism)
• Case-Control Studies
• Catenins (metabolism)
• Female
• Heart Rupture, Post-Infarction (etiology)
• Humans
• Intercellular Adhesion Molecule-1 (metabolism)
• Male
• Mice
• Middle Aged
• Models, Animal
• Myocardium (metabolism)
• Myocytes, Cardiac (metabolism)
• Risk Factors