title: New and Emerging Therapies and Targets: Beta-3 Agonists.
abstract: While crucial for the acute physiologic response to stress, the adrenergic system may become maladaptive upon prolonged stimulation in the course of development of heart failure. This has been the basis for the development of beta-blocking therapies, targeting mainly beta1-2 adrenoreceptors (B1-2AR). The third isotype, B3AR, was more recently identified in cardiac myocytes and endothelial cells from human (and many other animal species), where its distinctive coupling to nitric oxide and antioxidant pathways suggested potential protective properties that were unexploited so far. The observation of beneficial effects of B3AR expression/activation on myocardial remodeling and the availability of specific agonists for clinical use now open the way for directly testing the hypothesis in heart failure patients. We will briefly review the specificities of B3AR signaling in the context of the cardiovascular adrenergic system, the evidence supporting its beneficial effects and outline an ongoing clinical trial using the B3AR agonist, mirabegron in patients with/at risk of developing heart failure with preserved ejection fraction (HFpEF).
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Experimentale et Clinique (IREC), Université Catholique de Louvain, B1.53.09, 52 Ave. Mounier, 1200, Brussels, Belgium.
authors.forename: Lauriane Y M
authors.initials: LYM
authors.lastname: Michel
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Experimentale et Clinique (IREC), Université Catholique de Louvain, B1.53.09, 52 Ave. Mounier, 1200, Brussels, Belgium. jean-luc.balligand@uclouvain.be.|Department of Medicine, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, 10 Ave. Hippocrate, 1200, Brussels, Belgium. jean-luc.balligand@uclouvain.be.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D015398:Signal Transduction; D013844:Thiazoles / Q000627:therapeutic use*; D020257:Ventricular Remodeling
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D002395:Catecholamines; D022702:Receptors, Adrenergic, beta-3; D013844:Thiazoles; D009569:Nitric Oxide; C520025:mirabegron
keywords: Adrenergic receptor; Catecholamines; Heart failure; Hypertrophy; Nitric oxide; Remodeling