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Published on: February 13, 2019
CardioNet: a human metabolic network suited for the study of cardiomyocyte metabolism
Anja Karlstädt1, Daniela Fliegner, Georgios Kararigas
1Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Charitéplatz 1/Virchowweg 6, 10117 Berlin, Germany. anja.karlstaedt@charite.de
Insights
CardioNet models the human cardiomyocyte's metabolic network, revealing how nutrient supply impacts cardiac function. This systems biology approach aids understanding of heart metabolism for adequate cardiac output.
Area of Science:
- Biochemistry
- Systems Biology
- Cardiovascular Physiology
Background:
- Coronary circulation's oxygen and nutrient supply critically impacts cardiac performance.
- Nutrient profiles in coronary blood fluctuate with diet, exercise, starvation, and diabetes.
- Systems biology analysis of cardiac metabolism clarifies nutrient supply-demand relationships.
Purpose of the Study:
- To develop a comprehensive metabolic network model of the human cardiomyocyte.
- To investigate the influence of varying nutrient availability on cardiomyocyte metabolic functions.
- To understand the link between nutrient supply and cardiac output efficiency.
Main Methods:
- Reconstruction of a large-scale metabolic network for human cardiomyocytes.
- Incorporation of 1793 metabolic reactions and 560 transport processes across six cellular compartments.
- Application of flux balance analysis to simulate metabolic functions.
Main Results:
- CardioNet successfully models 368 essential metabolic functions for cardiomyocyte integrity.
- Analysis demonstrates how glucose, fatty acids, and ketone bodies affect ATP production and phospholipid biosynthesis.
- The model predicts the impact of altered nutrient supply on key cellular processes like ceramide and cardiolipin synthesis.
Conclusions:
- CardioNet provides a validated metabolic network for human cardiomyocytes.
- Enables theoretical exploration of cellular metabolism impacting cardiac output.
- Facilitates research into cardiac metabolic regulation and dysfunction.
Background:
Availability of oxygen and nutrients in the coronary circulation is a crucial determinant of cardiac performance. Nutrient composition of coronary blood may significantly vary in specific physiological and pathological conditions, for example, administration of special diets, long-term starvation, physical exercise or diabetes. Quantitative analysis of cardiac metabolism from a systems biology perspective may help to a better understanding of the relationship between nutrient supply and efficiency of metabolic processes required for an adequate cardiac output.
Results:
Here we present CardioNet, the first large-scale reconstruction of the metabolic network of the human cardiomyocyte comprising 1793 metabolic reactions, including 560 transport processes in six compartments. We use flux-balance analysis to demonstrate the capability of the network to accomplish a set of 368 metabolic functions required for maintaining the structural and functional integrity of the cell. Taking the maintenance of ATP, biosynthesis of ceramide, cardiolipin and further important phospholipids as examples, we analyse how a changed supply of glucose, lactate, fatty acids and ketone bodies may influence the efficiency of these essential processes.
Conclusions:
CardioNet is a functionally validated metabolic network of the human cardiomyocyte that enables theorectical studies of cellular metabolic processes crucial for the accomplishment of an adequate cardiac output.
