RESUMEN
Cardiac diseases, such as heart failure, remain leading causes of morbidity and mortality worldwide, with myocardial infarction as the most common etiology. HF is characterized by ß-adrenergic receptor (ßAR) dysregulation that is primarily due to the upregulation of G protein-coupled receptor kinases that leads to overdesensitization of ß1 and ß2ARs, and this clinically manifests as a loss of inotropic reserve. Interestingly, the "minor" ßAR isoform, the ß3AR, found in the heart, lacks G protein-coupled receptor kinases recognition sites, and is not subject to desensitization, and as a consequence of this, in human failing myocardium, the levels of this receptor remain unchanged or are even increased. In different preclinical studies, it has been shown that ß3ARs can activate different signaling pathways that can protect the heart. The clinical relevance of this is also supported by the effects of ß-blockers which are well known for their proangiogenic and cardioprotective effects, and data are emerging showing that these are mediated, at least in part, by enhancement of ß3AR activity. In this regard, targeting of ß3ARs could represent a novel potential strategy to improve cardiac metabolism, function, and remodeling.