Systems biology: An emerging strategy for discovering novel pathogenetic mechanisms that promote cardiovascular disease

Reductionist theory proposes that analyzing complex systems according to their most fundamental components is required for problem resolution, and has served as the cornerstone of scientific methodology for more than four centuries. However, technological gains in the current scientific era now allow for the generation of large datasets that profile the proteomic, genomic, and metabolomic signatures of biological systems across a range of conditions. The accessibility of data on such a vast scale has, in turn, highlighted the limitations of reductionism, which is not conducive to analyses that consider multiple and contemporaneous interactions between intermediates within a pathway or across constructs. Systems biology has emerged as an alternative approach to analyze complex biological systems. This methodology is based on the generation of scale-free networks and, thus, provides a quantitative assessment of relationships between multiple intermediates, such as protein-protein interactions, within and between pathways of interest. In this way, systems biology is well positioned to identify novel targets implicated in the pathogenesis or treatment of diseases. In this review, the historical root and fundamental basis of systems biology, as well as the potential applications of this methodology are discussed with particular emphasis on integration of these concepts to further understanding of cardiovascular disorders such as coronary artery disease and pulmonary hypertension.