Role of beta-adrenergic receptor signaling and desensitization in heart failure: new concepts and prospects for treatment.
The use of beta-blockers to antagonize beta-adrenergic receptor signaling in the heart has become a standard method of treatment for heart failure, resulting in positive clinical outcomes alone and in conjunction with other modulators of cardiomyocyte contractility. However, an entire explanation for improved cardiac function in patients using beta-blockers is unknown, and in fact may be quite complicated, considering the numerous intracellular signaling pathways associated with beta-adrenergic receptors. Stimulation of beta-adrenergic receptors during both normal conditions and during heart failure activate several distinct signaling cascades, which influence cardiomyocyte contraction, hypertrophy and apoptosis. This review explores the signaling cascades induced by beta-adrenergic receptor activation in normal and desensitized states to provide new insight into the effective treatment of cardiac dysfunction.
Tilley
Douglas G
DG
Department of Medicine Duke University Medical Center Durham, NC 27710, USA. douglas.tilley@duke.edu
Rockman
Howard A
HA
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D019390:Arrestins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D011110:Polymorphism, Genetic; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000071557:beta-Arrestins
D000319:Adrenergic beta-Antagonists; D019390:Arrestins; D011943:Receptors, Adrenergic, beta; D000071557:beta-Arrestins; D051606:G-Protein-Coupled Receptor Kinase 1; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases