Dysfunction of the ADP/ATP carrier as a causative factor for the disturbance of the myocardial energy metabolism in dilated cardiomyopathy.
The adenine nucleotide translocator (ADP/ATP carrier) plays a key role in nucleotide transport across the mitochondrial membrane. The quantity and function of this transport protein were investigated in myocardium from hearts with endstage failing dilated and ischemic cardiomyopathy, and were compared to measurements in nonfailing myocardium. In addition, lactate dehydrogenase (LDH) isoenzymes were determined. The concentration of the ADP/ATP carrier was significantly increased by 48% in myocardium from dilated cardiomyopathic hearts compared to control myocardium. The concentration of the carrier in explanted hearts with ischemic cardiomyopathy did not differ from values in the normal human hearts. Analysis of carrier function revealed similar nucleotide exchange rates in control hearts and hearts with ischemic cardiomyopathy, whereas carrier function was reduced in most hearts with dilated cardiomyopathy. Compared to control hearts, in hearts with dilated cardiomyopathy and decreased nucleotide exchange rate, the carrier content was significantly higher, whereas the carrier content was only slightly increased compared to control in cardiomyopathy hearts with unchanged transport activity. Compared to hearts, in dilated cardiomyopathy there was a significant increase in LDH5 and a decrease in LDH1 isoforms, indicating more anaerobic metabolism in failing dilated cardiomyopathic hearts. In summary, in hearts with dilated cardiomyopathy disturbed function of the ADP/ATP-carrier may result in altered myocardial energy metabolism and, thus, may be the cause of impaired myocardial function.
Schultheiss
H P
HP
Medical Clinic B, Dept. for Cardiology, Pneumology, and Angiology, Heinrich-Heine University, Düsseldorf, FRG.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D003327:Coronary Disease / Q000503:physiopathology*; D004734:Energy Metabolism; D006801:Humans; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques
D007527:Isoenzymes; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D007770:L-Lactate Dehydrogenase