Molecular mechanisms of cardiomyopathies


Cardiomyopathy is a socially significant disease that is characterized by a high disability rate at young age, development of sudden death syndrome and need for high-tech treatment methods such as heart transplantation and cardioverter defibrillator implantation. The significance of basic and applied research in this area is also defined by the requirement for translation and personalized medicine development as this would be the most prospective approach for the treatment of genetically caused diseases. In this regard, the development of more informative cellular technologies and the creation of an adequate cellular model for studying the pathogenesis of the serious genetically caused heart diseases are the main aims for current biomedical science.

During the previous years the research work has been mainly devoted to the study of the pathogenesis of cardiomyopathy associated with desmin and lamin genes. It was shown that the development basis for desmin myopaties and cardiomyopathies is caused by alterations in desmin filaments polymerization process as the result of desmin gene mutations. However, in some cases mitochondrial structural and functional alterations can precede the alterations in desmin filaments. Presently, alteration process in function of mitochondrial membrane as a result of desmin mutations is still poorly understood, but now it is already known that this process can be one of possible triggers in disease progression. This research area as well as studying of laminopathy pathogenesis is the subject of collaborative work with Karolinska Institute. Mutations in lamin A/C cause several serious diseases: cardiomyopathy, myodystrophy, familial lipodystrophy and progeria. Among post-heart transplant patients there is 10% with cardiomyopathies caused by lamin A/C mutations. The role of nuclear lamins in spatial organization of chromatin, gene regulation and process of signal transduction is already proved. Some data about influence of nuclear lamins on cell differentiation has been obtained, particularly, in mesenchymal tissue. In conclusion to all above, the research results can be used for the new approach for cell therapy of these serious diseases.