Functional consequences of altering myocardial adrenergic receptor signaling

被引:121
作者
Koch, WJ [1 ]
Lefkowitz, RJ
Rockman, HA
机构
[1] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Canc Biol, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA
[6] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA
关键词
gene-targeted mice; adrenergic receptors; G protein signaling; desensitization; heart failure;
D O I
10.1146/annurev.physiol.62.1.237
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
From the ability to successfully manipulate the mouse genome has come important transgenic and gene-targeted knockout models that impact many areas of biomedical research. Genetically engineered mouse models geared toward the study of cardiovascular regulation have recently been described and provide powerful tools to study normal and compromised cardiac physiology. The genetic manipulation of the adrenergic receptor (AR) signaling system in the heart, including its regulation by desensitizing kinases, has shed light on the role of this signaling pathway in the regulation of cardiac contractility. One major finding, supported by several mouse models, is that in vivo contractility can be enhanced via alteration of myocardial AR signaling. Thus genetic manipulation of this critical receptor system in the heart represents a novel therapeutic approach for improving function of the failing heart.
引用
收藏
页码:237 / 260
页数:24
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