Cardiovascular Networks

“If there is any area in which a network thinking could trigger a revolution, I believe that biology is it.” — Albert Laszlo Barabasi 1Traditional biological and biochemical studies deal with relatively few components, allowing intuitive reasoning to guide hypotheses and experiments. For example, a popular experimental protocol in cardiovascular research is to examine gene functions through the use of transgenic or gene-targeted mice. Although clearly informative, it is becoming increasingly clear that such studies alone are not sufficient to explain complex processes such as arrhythmias, heart failure, and atherogenesis. Even a basic behavior, the action potential of a cardiomyocyte, requires the coordinated actions of >20 different ion transporters and channels.2 Perturbing proteins individually will help establish their functions, but it will not provide a full understanding of how they function together (quantitatively, temporally, and spatially). For this, a more global analysis, in which the activities of all of the relevant proteins are tracked over time and then integrated into a quantitative mathematical model, is required to provide a deeper level of understanding of cardiomyocyte dynamics.A new branch of biology, called systems biology, seeks to identify the components of complex systems and to model their dynamic interactions.3 The approach arose in large part as a result of new technical and analytical developments. The Human Genome Project provided a biological “parts list,” and technologies such as massively parallel DNA sequencing, expression microarrays, and tandem mass spectrometric analyses of proteins and metabolites have made high-throughput analysis of biological systems feasible. To deal with the data explosion, novel statistical and other mathematical modeling approaches are being developed.Basically, systems-based approaches involve 4 steps. The first is to define the system to be examined (eg, a cardiomyocyte). The second is to identify the components of the system (eg, the set …