Abstract
Common cardiovascular diseases, such as atherosclerosis and congestive heart failure, are exceptionally complex, involving a multitude of environmental and genetic factors that often show nonlinear interactions as well as being highly dependent on sex, age, and even the maternal environment. Although focused, reductionistic approaches have led to progress in elucidating the pathophysiology of cardiovascular diseases, such approaches are poorly powered to address complex interactions. Over the past decade, technological advances have made it possible to interrogate biological systems on a global level, raising hopes that, in combination with computational approaches, it may be possible to more fully address the complexities of cardiovascular diseases. In this Review, we provide an overview of such systems-based approaches to cardiovascular disease and discuss their translational implications.
Key Points
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The cardiovascular system is a complex network of organs and cell types, each with specialized, but highly coordinated, functions; therefore, cardiovascular disease is complex in etiology and manifestation
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A systems-based approach aims to reveal the architecture and the emerging properties of a complex network by uncovering the relationships among the constituents and establishing global governing principles
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Current advances in bioinformatics, genomics, proteomics, and metabolomics offer an excellent opportunity to use systems-based analysis to dissect complex networks involved in cardiovascular physiology and diseases
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In the study of cardiovascular diseases, systems biology compliments genetic analyses, such as genome-wide association studies, by establishing the underlying mechanisms and the functional significance of the candidate genes
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'Systems genetics' is a new approach based on the systems-based analysis of genetic variants and phenotypic spectra at various levels, spanning from gene expression to organ physiology
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By establishing the molecular components and gene networks for the cardiovascular system, systems biology can help to develop effective and personalized diagnostic tools and therapies for cardiovascular diseases
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MacLellan, W., Wang, Y. & Lusis, A. Systems-based approaches to cardiovascular disease. Nat Rev Cardiol 9, 172–184 (2012). https://doi.org/10.1038/nrcardio.2011.208
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DOI: https://doi.org/10.1038/nrcardio.2011.208
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