VENTRICULAR ADENINE-NUCLEOTIDE TRANSLOCATOR MESSENGER-RNA IS UP-REGULATED IN DILATED CARDIOMYOPATHY

Objective: A disturbed energy transfer involving the adenine nucleotid e translocator across the inner mitochondrial membrane has been sugges ted to be one specific pathogenetic mechanism in dilated cardiomyopath y. Pretranslational steady state expression of this protein in dilated cardiomyopathy was investigated. Methods: Concentrations of adenine n ucleotide translocator were quantified by solution hybridisation. The enzyme or protein expressions of citrate synthase, lactate dehydrogena se, and creatine kinase with isozymes were determined. Analysis was pe rformed on specimens from the left and right ventricles from six organ donor hearts, six explanted hearts with dilated cardiomyopathy, two e xplanted hearts with ischaemic cardiomyopathy, and from papillary musc les from seven patients operated on for mitral regurgitation. Results: The ejection fraction in patients with mitral regurgitation was 50(10 )%, significantly higher (p<0.001) than in patients with dilated cardi omyopathy (23(5))%. In mitral regurgitation and in ischaemic cardiomyo pathy left ventricular adenine nucleotide translocator mRNA concentrat ions did not differ from those in donor hearts. In dilated cardiomyopa thy, adenine nucleotide translocator mRNA concentrations were signific antly increased (p<0.001). Upregulation was more pronounced in right v entricular than in left ventricular myocardium (p<0.01). The lactate d ehydrogenase M subunit fraction was increased to a similar degree in d ilated cardiomyopathy and in mitral regurgitation (p<0.05). Citrate sy nthase activity was significantly decreased only in dilated cardiomyop athy (p<0.005). On the other hand, the creatine kinase B subunit conte nt was significantly higher in mitral regurgitation than in dilated ca rdiomyopathy (p<0.001). Conclusions: Despite signs of increased anaero bic and depressed oxidative capacities, dilated cardiomyopathy was spe cifically characterised by pretranslational upregulation of adenine nu cleotide translocator.