Systems Medicine to dissect the Biology of Heart Failure

Human heart failure (HF) is the leading cause of hospitalization in Germany and other Western world countries and is associated with high morbidity and mortality thereby putting a large burden on our health care costs. However, up to date the molecular underpinnings of HF are only poorly defined, but are essential for the development of targeted therapies. In search for the common molecular network of HF the members of this consortium (SYMBOL-HF) already established and characterized by “omics” technologies a large variety of heart failure models in zebrafish, mice, and humans. In addition, they developed novel bioinformatic methods that allow the systematic analysis of large transcriptome datasets species-specific and cross-species.

Organization of SYMBOL-HF including the interactions between the subprojects. Arrows depict iterative cycles of data analysis and validation.

In order to decipher for the first time the common molecular denominators of HF this consortium will

  • first subject their large transcriptome datasets from the various HF models to a combined bioinformatics analysis.
  • Secondly, the transcriptome networks derived from these analyzes will be validated in established cardiomyocyte systems (primary and iPS), animal models (zebrafish, mouse), and in human tissue.
  • Finally, to enable targeted therapies for human HF novel HF network components and especially hub nodes will be tested for their drugability in vitro and in vivo.

Subprojects in SYMBOL-HF:

Sp 1   Functional genomics in zebrafish to dissect the molecular networks of heart failure

Sp 2   Integration of mechanotransduction and pathogenesis of dilated cardiomyopathy and heart failure

SP 3   Functional Genomics in Human Heart Failure

SP 5   Cross-species model analysis of heart disease regulation