Adrenergic regulation of cardiac myocyte apoptosis

✍ Scribed by Krishna Singh; Lei Xiao; Andrea Remondino; Douglas B. Sawyer; Wilson S. Colucci

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 156 KB
• Volume: 189
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.10024

✦ Synopsis

Abstract

The direct effects of catecholamines on cardiac myocytes may contribute to both normal physiologic adaptation and pathologic remodeling, and may be associated with cellular hypertrophy, apoptosis, and alterations in contractile function. Norepinephrine (NE) signals via α‐ and β‐adrenergic receptors (AR) that are coupled to G‐proteins. Pharmacologic studies of cardiac myocytes in vitro demonstrate that stimulation of β~1~‐AR induces apoptosis which is cAMP‐dependent and involves the voltage‐dependent calcium influx channel. In contrast, stimulation of β~2~‐AR exerts an anti‐apoptotic effect which appears to be mediated by a pertussis toxin‐sensitive G protein. Stimulation of α~1~‐AR causes myocyte hypertrophy and may exert an anti‐apoptotic action. In transgenic mice, myocardial overexpression of either β~1~‐AR or Gαs is associated with myocyte apoptosis and the development of dilated cardiomyopathy. Myocardial overexpression of β~2~‐AR at low levels results in improved cardiac function, whereas expression at high levels leads to dilated cardiomyopathy. Overexpression of wildtype α~1B~‐AR does not result in apoptosis, whereas overexpression of Gαq results in myocyte hypertrophy and/or apoptosis depending on the level of expression. Differential activation of the members of the mitogen‐activated protein kinase (MAPK) superfamily and production of reactive oxygen species appear to play a key role in mediating the actions of adrenergic pathways on myocyte apoptosis and hypertrophy. This review summarizes current knowledge about the molecular and cellular mechanisms involved in the regulation of cardiac myocyte apoptosis via stimulation of adrenergic receptors and their coupled effector pathways. © 2001 Wiley‐Liss, Inc.