β-Adrenergic receptor subtype signaling in heart： From bench to bedside

• Published in: Acta pharmacologica Sinica Vol. 33; no. 3; pp. 335 - 341
• Main Authors: Woo, Anthony Yiu Ho, Xiao, Rui-ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2012; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; GTP-Binding Proteins - metabolism; Humans; Immunology; Internal Medicine; Medical Microbiology; Myocytes, Cardiac - metabolism; Pharmacology/Toxicology; Receptors, Adrenergic, beta - classification; Receptors, Adrenergic, beta - metabolism; Review; Signal Transduction; Vaccine; 交感神经系统; 儿茶酚胺; 受体亚型; 心肌细胞; 心脏结构; 肾上腺素受体; 血液循环; 重构信号; heart failure; cardiovascular system; β-adrenergic receptor; signal transduction
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2011.201

β-Adrenergic receptor （βAR） stimulation by the sympathetic nervous system or circulating catecholamines is broadly involved in peripheral blood circulation, metabolic regulation, muscle contraction, and central neural activities. In the heart, acute βAR stimulation serves as the most powerful means to regulate cardiac output in response to a fight-or-flight situation, whereas chronic βAR stimulation plays an important role in physiological and pathological cardiac remodeling. There are three βAR subtypes, β1AR, β2AR and β2AR, in cardiac myocytes. Over the past two decades, we systematically investigated the molecular and cellular mechanisms underlying the different even opposite functional roles of β1AR and β2AR subtypes in regulating cardiac structure and function, with keen interest in the development of novel therapies based on our discoveries. We have made three major discoveries, including （1） dual coupling of β2AR to Gs and Gs proteins in cardiomyocytes, （2） cardioprotection by β2AR signaling in improving cardiac function and myocyte viability, and （3） PKA-independent, CaMKII-mediated β1AR apoptotic and maladaptive remodeling signaling in the heart. Based on these discoveries and salutary effects of βAR blockade on patients with heart failure, we envision that activation of 1β2AR in combination with clinically used β1AR blockade should provide a safer and more effective therapy for the treatment of heart failure.