‘Integrative Physiology 2.0’: integration of systems biology into physiology and its application to cardiovascular homeostasis

Abstract

Since the completion of the Human Genome Project and the advent of the large scaled unbiased '-omics' techniques, the field of systems biology has emerged. Systems biology aims to move away from the traditional reductionist molecular approach, which focused on understanding the role of single genes or proteins, towards a more holistic approach by studying networks and interactions between individual components of networks. From a conceptual standpoint, systems biology elicits a 'back to the future' experience for any integrative physiologist. However, many of the new techniques and modalities employed by systems biologists yield tremendous potential for integrative physiologists to expand their tool arsenal to (quantitatively) study complex biological processes, such as cardiac remodelling and heart failure, in a truly holistic fashion. We therefore advocate that systems biology should not become/stay a separate discipline with '-omics' as its playing field, but should be integrated into physiology to create 'Integrative Physiology 2.0' .

Impact of exercise training on endothelial transcriptional profiles in healthy swine: a genome-wide microarray analysis

“…While these reductionist approaches have represented a crucial forward step towards our understanding of the impact of physical activity on vascular cells, it is important to recognize that, by nature, they are insufficient to provide us with a wide appreciation of the complex molecular effects of exercise. As a result, there is a need to move toward more holistic and integrative molecular approaches (26).…”

“…This program allows the unbiased construction of gene (product) networks of interacting molecules by connecting all possible differentially expressed genes and hub molecules (molecules of which the expression remains unchanged; Ref. 26). Figure 5 illustrates the top endothelial gene networks influenced by exercise training in the brachial and internal mammary arteries.…”

A conceptual paradigm of heart failure and systems biology approach

“…Kuster et al [12], in a porcine model of myocardial infarction studied swine at rest and during graded treadmill exercise, with the intention of recruiting the cardiac and coronary functional reserve capacity, and probing into the compensatory mechanisms responsible for the maintenance of cardiovascular homeostasis. This study showed that myocardial oxygen balance was mildly perturbed in the remodeled myocardium due to the plasticity of the post-myocardial infarction remodeled heart and coronary circulation, and that the experimental results were explored in an integrative approach in an intact porcine model.…”

“…An example of integrative approach observing at the whole system and not only to the interaction of the individual elements, is the study of the coronary control mechanisms in cardiac remodeling after myocardial infarction [12]. Kuster et al [12], in a porcine model of myocardial infarction studied swine at rest and during graded treadmill exercise, with the intention of recruiting the cardiac and coronary functional reserve capacity, and probing into the compensatory mechanisms responsible for the maintenance of cardiovascular homeostasis.…”

“…It seems that the discipline of systems biology will provide the necessary scientific tools to understand human heart failure and its complex processes that are involved. Kuster et al [12], advocate that systems biology should not become a separate discipline with "omics" as its main field of action, but should be integrated into physiology under the name of "Integrative Physiology 2.0". On the other hand, Greenhaff and Hargreaves [13] believe that at the present time systems biology "is rooted in processes operating at a cellular level" and that there are "conceptual inconsistencies between the fields of systems biology and integrative physiology in the context of exercise science".…”