Mitochondrial DNA mutations and mitochondrial abnormalities in dilated cardiomyopathy
E Arbustini1, M Diegoli, R Fasani
1Cardiovascular Pathology and Molecular Diagnostic, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy. e.arbustini@smatteo.pv.it
The American Journal of Pathology
|November 12, 1998
Summary
Pathological mitochondrial DNA (mtDNA) mutations are linked to specific ultrastructural abnormalities in cardiac mitochondria. These defects are found in a subset of dilated cardiomyopathy patients and are associated with reduced cytochrome c oxidase activity.
Area of Science:
- Cardiology
- Genetics
- Mitochondrial Biology
Background:
- Mitochondrial DNA (mtDNA) mutations, including deletions and tRNA point mutations, are implicated in cardiomyopathies.
- Dilated cardiomyopathy (DCM) is a complex heart condition where mitochondrial dysfunction may play a role.
Purpose of the Study:
- To determine the prevalence of pathological mtDNA mutations in DCM patients exhibiting specific ultrastructural mitochondrial abnormalities.
- To assess the impact of these mutations on mitochondrial enzyme activity in cardiac tissue.
Main Methods:
- Analysis of endomyocardial biopsy samples from 601 DCM patients using light and electron microscopy.
- Screening for mtDNA mutations (tRNA, rRNA, missense) using DNA sequencing and restriction enzyme digestion in selected cases.
- Quantification of mutant mtDNA levels in myocardial and blood DNA and assessment of mitochondrial enzyme activities (cytochrome c oxidase, NADH dehydrogenase, succinic dehydrogenase).
Main Results:
- Ultrastructural abnormalities were observed in 85 DCM patients, 22.35% of whom had heteroplasmic mtDNA mutations not found in controls.
- Mutant mtDNA levels were consistently higher in heart tissue than in blood.
- Reduced cytochrome c oxidase activity was significantly associated with mtDNA mutations in DCM patients.
Conclusions:
- Morphological identification of abnormal cardiac mitochondria can serve as a marker for guiding mtDNA mutation screening in DCM.
- Pathological mtDNA mutations are associated with specific mitochondrial abnormalities and reduced enzyme activity in a subset of idiopathic DCM patients.
- mtDNA defects may contribute to the pathogenesis of congestive heart failure in these patients.
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