title: Cardiac salvage by tweaking with beta-3-adrenergic receptors.
abstract: Overstimulation of the orthosympathetic system leads to cardiovascular cell and tissue damage through prolonged activation of β-1-2 adrenergic receptors (BARs). The more recent identification of the third isotype of BAR (B3AR) in cardiac myocytes and endothelial cells with a distinctive coupling and effect on cardiac function and remodelling introduced a new facet to this paradigm. In particular, B3AR is up-regulated in cardiac disease and less prone to homologous desensitization, which may reinforce its influence on the diseased myocardium. Mice with transgenic cardiac-specific expression of the human B3AR are protected from cardiac hypertrophy and fibrosis in response to neurohormonal stimulation. B3AR has also been implicated in cardiac protection after ischaemia-reperfusion and the benefits of exercise on the heart. Many of these salvage mechanisms are mediated by B3AR coupling to nitric oxide synthase (eNOS and nNOS) and downstream cGMP/protein kinase G signalling. Notably, B3AR exerts antioxidant protective effects on these and other signalling elements, which may subserve its protective properties in the setting of chronic heart failure. Additional vasorelaxing properties and paracrine NO-mediated signalling by B3AR in endothelium, together with systemic metabolic effects on beige/brown fat complete the pleiotropic protective properties of this new therapeutic target.
authors.affiliation: Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Experimentale et Clinique (IREC), and Department of Medicine, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, B1.53.09, 52 avenue Mounier, 1200 Brussels, Belgium jl.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; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000627:therapeutic use; D020257:Ventricular Remodeling
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D022702:Receptors, Adrenergic, beta-3; D013844:Thiazoles; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; C520025:mirabegron
keywords: adrenergic receptor; catecholamines; heart failure; hypertrophy; nitric oxide; remodelling