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 deletions in the mtDNA of patients with dilated cardiomyopathy (DCM) and post mortem control samples. Total DNA was extracted from left ventricular tissue and nearly the whole mtDNA was amplified using the long PCR technique. For quantitative analysis of the PCR-products with mtDNA deletions the fragments were scanned by a laser 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 could be detected. The highest rate of deleted as compared to wild-type mtDNA 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 control hearts. With regard to the low quantity of the deleted mtDNA and the cumulative nature of these deletions by ageing, we conclude that they may be relevant in individual cases only. A general pathogenic effect on the development of dilated cardiomyopathy is less likely. The mutations may be a sign of increasing stress to the heart, however, thus promoting consecutive damage of mtDNA by initiating a vicious circle.