Defective intercellular adhesion complex in myocardium predisposes to infarct rupture in humans.
OBJECTIVE
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.
Department of Pharmacology and Toxicology and Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Susanne W M
SW
van den Borne
Jagat
J
Narula
J Willem
JW
Voncken
Peter M
PM
Lijnen
Helena T M
HT
Vervoort-Peters
Vivian E H
VE
Dahlmans
Jos F M
JF
Smits
Mat J A P
MJ
Daemen
W Matthijs
WM
Blankesteijn
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002102:Cadaver; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D051177:Catenins / Q000378:metabolism; D005260:Female; D006342:Heart Rupture, Post-Infarction / Q000209:etiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012307:Risk Factors
D015820:Cadherins; D051177:Catenins; D018799:Intercellular Adhesion Molecule-1