The role of G-protein-coupled receptors in heart failure

Pascal J. Goldschmidt-Clermont—Duke University Medical Center, Durham, NC, USA Heart failure is the fastest growing cardiovascular condition in Westernized countries. It is associated with substantial disability, morbidity, mortality and cost. β-Blocker drugs form the basis of treatment for congestive heart failure. They inhibit cardiac adrenergic drive and allow re-sensitization of β-adrenoceptors (βARs) – prototypical G-protein-coupled receptors (GPCRs) that are otherwise downregulated in heart failure. Rockman and his group are credited for much of our understanding of βARs and downstream signal transduction mechanisms, having performed preclinical experiments on genetically engineered murine models that reproduce human conditions and hemodynamic monitoring. This review provides a critical appraisal of GPCR signaling and regulatory mechanisms that are paramount in understanding heart failure pathophysiology and in developing new approaches for its treatment.