Molecular pathogenesis of severe cardiomyopathy in the TO-2 hamster.
BACKGROUND
Cardiomyopathy (CM) is a life-threatening disease with progressive degeneration of cardiac muscle. From a representative animal model of CM, the BIO14.6 hamster, arose the TO-2 strain manifesting a severe, dilated form of CM. Previous studies demonstrated that both strains have an identical genomic deletion disrupting the delta-sarcoglycan gene to cause CM.


OBJECTIVE
To elucidate an additional pathogenesis for cardiac dilation in the TO-2 hamster.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) was used to assess the expression levels of genes for cardiac hypertrophy, such as beta-myosin heavy chain and preproendothelin-1. The involvement of apoptosis in CM was tested using terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labelling (TUNEL) and DNA ladder assays. The progression of cardiac degeneration was visualized using specific histological staining techniques. Echocardiography was performed to estimate the wall thickness and the movement of a living hamster heart.


RESULTS
RT-PCR showed the expression of the genes involved in cardiac hypertrophy to be higher in TO-2 hamsters than in BIO14.6 hamsters, contary to what the thin myocardium may suggest. DNA ladder and TUNEL assays showed no significant difference in apoptosis in the hearts of either strain. In contrast, the infiltrate of inflammatory cells was prominent in the myocardium of TO-2 hamsters. In addition to dilation of the cardiac chamber, echocardiography also revealed disharmonized contraction in TO-2 hearts without apparent arrhythmias.


CONCLUSIONS
Impairment of compensatory cardiac hypertrophy or involvement of apoptosis is less likely to be an additional pathogenesis in the TO-2 hamster. The present data suggest that augmented necrosis is the principal cause of severe CM in the TO-2 hamster. Further analysis of the molecular pathogenesis of TO-2 would help to disclose the final common pathways for the manifestation of CM.
Sakamoto
Aiji
A
Division of Biotechnology, National Cardiovascular Center Research Institute, Osaka, and Form and Function, PRESTO, Japan Science and Technology Agency, Saitama, Japan.