Genomics and the pathophysiology of heart failure

Heart failure is not a single disease entity, but a syndrome with various causes, including hypertension, ischemic and congenital heart disease, cardiomyopathy, and myocarditis. Because of the multiple etiologies and secondary adaptations contributing to heart failure, the study of the cellular and molecular mechanisms underlying the development and progression of this syndrome has been rather challenging. Much has been learned about the remodeling processes in heart failure, which involve complex interactions among numerous mediators in signaling and regulatory pathways. The Human Genome Project and related projects have provided a preliminary database for a genome-wide analysis of complex polygenic disorders such as heart failure. With the aid of expressed sequence tag technology and microarray applications, both known and previously uncharacterized genes involved in the induction and regression of cardiac hypertrophy and its progression to heart failure can be analyzed simultaneously. Deciphering the complexity of sequence-structure-function relationships in heart failure is a goal for the future, and will require advances in structural biology, proteomics, and computational technology. In this review, we summarize the cellular and molecular aspects of heart failure, and how recent applications of genomic technologies have been successful in achieving a more complete portrait of gene expression in this pathologic state.