Heart Failure Transcriptome

Abstract

The article by Barth et al1 in this issue points to a critical facet in heart failure investigation, namely, the molecular divergence observed between preclinical models of disease and clinical authenticity. These authors compared gene expression patterns from hearts of human, dogs, and rodents.1 Women and men appear to differ from mice in respect to the transcriptome dynamics of the failing heart. Not surprised? The implications of this finding may be potentially game changing for the future design of translational strategies to advance discovery science into patient care. Article see p 475 Heart failure is a significant health problem, affecting nearly 1 in 5 adults, with a cost of >$40 billion per year.2 Barth et al present data from a meta-analysis of several studies to suggest that the gene expression patterns in preclinical animal models of heart failure are significantly different than those in human heart failure.1 Specifically, Barth et al show that the significant downregulation of metabolic signaling pathways and reciprocal upregulation of cell signaling in rodent and dog models are not found in all human heart failure specimens.1 If dissimilar patterns in gene expression reflect different pathophysiological characteristics, the current course of testing new therapies for human heart failure in rodent and dog models may be questioned. Modeling heart failure in rodents and dogs is typically performed on an accelerated time course compared with natural disease progression in humans. The gene expression changes seen in pre-clinical models of heart failure in this study may more closely simulate acute heart failure syndrome3,4 versus chronic heart failure. Chronic human heart failure may present with changes referred to as remodeling and include dilatation of the ventricular …