CardioNet: A human metabolic network suited for the study of cardiomyocyte metabolism

Abstract

BackgroundAvailability 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.ResultsHere 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.ConclusionsCardioNet 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.

Oncometabolite d -2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart

“…To understand whether overproduction of D2-HG alone was responsible for the effects observed in the Idh2 mutant mouse model, we measured rates of substrate metabolism in the isolated working rat heart and conducted computational flux rate analysis using the CardioNet model of mammalian cardiac metabolism (14). Rat hearts were perfused ex vivo in the presence or absence of D2-HG in concentrations similar to those found in the plasma of Idh2 R140Q mutant mice (0.5 mM) and AML patients (8,(15)(16)(17) and those reported by Latini et al (18) to promote inhibition of ATP synthase in cardiac muscle in vitro (range 0.05-5 mM; F 0 /F 1 ATP synthase K i = 0.47 ± 0.18 mM) (Fig.…”

A mobile application for ECG detection and feature extraction

“…Traditional ECG tests are done in a special medical institution with the proper equipment and with professional medical personnel who will read the results and look for patterns and problems with the activity of the patient's heart. Recently, with the advent of new advanced portable and wireless technologies, the medical institution need not be the only place where ECG tests are conducted [2]. With the advancements these technologies, we are able to detect the risk of heart attack occurrence, and with a timely medical attention potentially reduce the number of heart attacks and their impact to the patients at a global level.…”

“…Several improvements for this problem are provided. Some of them are data recorders such as Holter [1] or Cardionet [2]. These improvements use a lot of loose cables that are attached to the body in order to connect the device to multiple ECG electrodes.…”

Challenges for development of an ECG m-Health solution

“…Some of them are data recorders such as Holter [10] or Cardionet [8]. These improvements use a lot of loose cables that are attached to the body in order to connect the device to multiple ECG electrodes.…”

“…New emerging technologies enable production of portable and wireless sensors and a medical institution will not be the only place where ECG tests are conducted [8]. These new technology gadgets do not obstruct physical movements as they are patches on the human body.…”