Mitochondrial defects at the biochemical and molecular levels are increasingly recognized in diseases involving the heart. The objective of this study was to assess the frequency and extent of mitochondrial defects in idiopathic dilated cardiomyopathy. Left ventricular tissues of 27 patients with idiopathic dilated cardiomyopathy undergoing orthotopic cardiac transplantation because of severe cardiac failure were examined to assess the specific activity levels of mitochondrial respiratory enzymes and changes in mtDNA structure and copy number. Abnormal specific activities of several mitochondrial enzymes were found in 55% of the cardiomyopathic tissues examined (15 patients), with six patients displaying single enzyme defects, including five in complex III and one in complex I. Multiple mitochondrial enzyme defects were found in nine patients, with the most frequent combination of defects seen in complex III and complex IV (5 cases). These enzymatic changes were shown not to be accompanied by changes in mtDNA copy number. In seven cases, however, including three young adults, there was a marked decrease in the levels of polymerase chain reaction products derived from specific mtDNA regions, which may be an indication of specific mtDNA damage. Specific mitochondrial abnormalities are frequently found in idiopathic dilated cardiomyopathy, with a variety of mitochondrial loci affected. These findings are not age dependent.
Bibliographical noteFunding Information:
Supported in part by grants from the St. Barnabas Medical Research Foundation, Livingston, NJ, and from the Gunshoots Program, Variety Club Association, Minneapolis, MN. Manuscript received Jan. 10, 1995; revised manuscript received April 12,1995; accepted April 28, 1995. Reprint requests: Jose Marin-Garcia, MD, The Molecular Cardiology Institute, 75 Raritan Avenue, Highland Park, NJ 08904.
- dilated cardiomyopathy
- mitochondria/mitochondrial DNA