title: Systems biology of heart failure, challenges and hopes.
abstract: OBJECTIVE
  Heart failure remains a leading cause of morbidity and mortality in developed nations. Our current understanding of molecular pathways involved in heart failure reveals little of the multiscale biological systems at work. Here we consider recent advances in understanding the integrative multiscale biology, or systems biology, of heart failure and present a framework for future work in the area.
  
  
  RESULTS
  Multiplexed assays of gene expression and the complex dynamics of protein-protein interactions in heart failure have illuminated key pathways important to myocardial adaptation. Modeling of complex systems has advanced to incorporate these dynamic data sources into networks that capture fundamental interactions on different biological scales. The complex syndrome of heart failure, like other complex disease syndromes, can be viewed as an emergent property of these multiscale systems.
  
  
  CONCLUSIONS
  A comprehensive understanding of adaptive mechanisms in heart failure requires integration of multiple data sources on several biological scales. A combination of holistic systems biology approaches and traditional reductionist experimentation will be required for a nuanced understanding of this multifaceted disease process.
authors.affiliation: Division of Cardiovascular Medicine, Stanford Hospital and Clinics, Stanford, California, USA.
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Dewey
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Wheeler
authors.forename: Euan A
authors.initials: EA
authors.lastname: Ashley
mesh_terms: D015415:Biomarkers; D006333:Heart Failure / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D016571:Neural Networks, Computer; D040901:Proteomics
chemical_list: D015415:Biomarkers