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Cardiac energetics in silico: micro-compartmentation of adenine nucleotides and the cross talk between organelles


Ischemic cardiomyopathy and heart failure represent a leading cause of degradation of quality of life and death in EU countries. Although major advances have been made in the treatment of coronary artery disease and heart failure, the mechanism of these my ocardial disorders remains poorly understood.

The general aim of this project is to study alternations of mitochondrial energetics, micro-compartmentation of adenine nucleotides, the crosstalk between intracellular organelles and cellular energy transfer in health and disease using mathematical modeling.

The specific goals of this project are
- to describe microcompartmentation of adenine nucleotides and the crosstalk between organelles in the cardiac muscle cells and
- to apply the knowledge acquired in studies of isolated mitochondria and skinned cardiac cells to analyze energy transfer in the beating heart.

For this, we will continue our mathematical modeling of intracellular energy transfer and analyze the energy fluxes estimated for beating heart. The research will be performed in tight cooperation with several national and EU laboratories. The expected results are as follows. Firstly, through application of mathematical modeling in analysis of the experimental data provided by our collaborators, we expect to clarify localization and the role of intracellular diffusion restrictions in the formation of microcompartments in cardiac muscle cells.

Secondly, by applying the knowledge acquired in studies of isolated mitochondria and skinned cardiac muscle cells to analyze energy transfer in the beating heart, we should be able to clarify the mechanisms underlying the modification of the energy pathways in normal beating hearts and in the hearts with partly inhibited ATP synthase. From clinical perspective, the developed models and algorithms are expected to provide the possibility to detect alterations in energy transfer pathways in vivo.

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Akadeemia 21

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