β-Adrenergic linked signal transduction mechanisms in failing hearts

被引：13

作者：

Dhalla N.S. ^{[1
]}

Wang X. ^{[1
]}

Sethi R. ^{[1
]}

Das P.K. ^{[1
]}

Beamish R.E. ^{[1
]}

机构：

[1] Institute of Cardiovascular Sciences, St. Boniface General Hospital, Research Centre, Winnipeg, Man. R2H 2A6

来源：

Heart Failure Reviews | 1997年 / 2卷 / 1期

关键词：

α-Adrenoceptors; Adenylyl cyclase; G-proteins; Heart failure; Signal transduction;

D O I：

10.1023/A:1009719404764

中图分类号：

学科分类号：

摘要：

The failing heart exhibits an attenuated response to adrenergic stimulation as a result of alterations in the function of β-adrenergic signal transduction pathway. Such changes include down-regulation of the β1-adrenoceptors, uncoupling of β-adrenoceptor from adenylyl cyclase, and an increase in the functional activity of G1-proteins. These changes are not homogeneous in all types of heart failure, but there is a good correlation between alterations in one or more components of β-adrenergic receptor complex and the severity of heart failure. Accordingly, patients with different types of heart muscle disease have been observed to exhibit some important pathophysiological differences despite common clinical features. By using specific antibodies and cDNA probes and a combination of molecular approaches, it is now possible to detect the protein and mRNA level of different components and various regulators of the β-adrenoceptor-G protein- adenylyl cyclase system. Instead of the traditional hypothesis that the β- adrenoceptor down-regulation in heart is due to abnormal degradation and synthesis of receptor proteins, it has now become evident that alterations in the β-receptor signal pathway may be due to transcriptional and posttranscriptional abnormalities in different components of failing hearts from both humans and animals. In addition, the availability of transgenic animals is facilitating the study of effects of altering a single component of the β-adrenergic system on the function of the heart regardless of the complexity of the system itself; the work in this area may make it possible to develop gene therapy for human heart failure.

引用

页码：55 / 65

页数：10

共 105 条

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