Mitochondrial DNA deletions in cardiomyopathies

Structural changes in the mitochondrial DNA (mtDNA) have been implicated in the pathogenesis of a number of diseases. In this study we report on delet ions in the mtDNA of patients with dilated cardiomyopathy (DCM) and post mo rtem control samples. Total DNA was extracted from left ventricular tissue and nearly the whole m tDNA was amplified using the long PCR technique. For quantitative analysis of the PCR-products with mtDNA deletions the fragments were scanned by a la ser densitometer. With the method of long PCR we could detect wild-type and deleted mtDNA in 1 reaction. A total of 14 different deletions ranging from 3.3 to 12.6 kb c ould be detected. The highest rate of deleted as compared to wild-type mtDN A was 12% in 1 control and 9% in a patient with dilated cardiomyopathy. The number of mitochondrial deletions increase with age in the control group. Additional deletions appear sooner in cardiomyopathic hearts than in contro l hearts. With regard to the low quantity of the deleted mtDNA and the cumulative nat ure of these deletions by ageing, we conclude that they may be relevant in individual cases only. A general pathogenic effect on the development of di lated cardiomyopathy is less likely. The mutations may be a sign of increas ing stress to the heart, however, thus promoting consecutive damage of mtDN A by initiating a vicious circle.