INSTITUTE OF PHYSIOLOGY CAS - The role of mitochondria in heart failure

To shed more light on whether OXPHOS defects can play a role in the development of heart failure, we analyse samples from patients undergoing heart transplants. We search for characteristic markers, which would be suitable for identification of new patients, as well as new potential targets for treatment.

Chronic heart failure

Chronic heart failure is one of the civilization diseases that is spreading in the developed countries. There are two reasons – aging of the population and a higher incidence of metabolic risks (obesity and diabetes). Therefore, the topics current research focuses on include studying the developmental mechanisms of heart failure and searching for new treatment procedures. Defects of energy production in mitochondria represent a very important factor because the heart has extremely high demands for energy supply.

Heteroplasmy
Every mitochondrion contains more than one molecule of mitochondrial DNA (mtDNA). The situation when all mtDNA molecules are the same is called homoplasmy. Heteroplasmy means that a mitochondrion contains a mix of normal and mutated mtDNA molecules. The ratio between mutated and normal mtDNA molecules determines the degree of heteroplasmy.

Goals of the project

Our new project in collaboration with the Institute of Clinical and Experimental Medicine (IKEM, Prague) is aimed to clarify how often abnormalities of mitochondrial energy-producing apparatus are present in the myocardium of patients suffering from developed heart failure. We also want to study mechanisms that lead to its development. Specifically, we are going:

To study alterations in the function and structure of energy-producing apparatus in mitochondria
To analyse the relationship between these alterations and the number of mtDNA copies
To look for somatic (created during one’s life) and inherited pathogenic mtDNA mutations
To investigate whether their incidence or their degree of heteroplasmy affect the level of oxidative damage of mitochondrial components

In the case of patients who lived with the ventricular assist device, we are going to study the effects of this treatment on mitochondrial bioenergetics.

Potential results

New findings for shedding light on the pathogenesis of severe myocardial defects.
Implementation of new diagnostic methods if we succeed in finding characteristic markers for identification of new patients in an early stage of disease.
Development of new treatment if we find new therapeutic targets.

The OROBOROS oxygraph for measurements of oxygen consumption by heart mitochondria is an important method for analysis of mitochondrial function in the heart.