Altered cAMP-mediated signalling and its role in the pathogenesis of dilated cardiomyopathy

被引:16
作者
Movsesian, MA
机构
[1] Univ Utah, Cardiol Sect, VA Salt Lake City Hlth Care Syst, Dept Internal Med Cardiol, Salt Lake City, UT 84148 USA
[2] Univ Utah, Cardiol Sect, VA Salt Lake City Hlth Care Syst, Dept Pharmacol, Salt Lake City, UT 84148 USA
关键词
altered cAMP-mediated signalling; dilated cardiomyopathy; protein kinase A;
D O I
10.1016/j.cardiores.2004.01.035
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Alterations in the level and function of proteins involved in cAMP-mediated signalling are important in the pathophysiology and treatment of dilated cardiomyopathy. What is unclear is the extent to which these alterations, which attenuate receptor-stimulated cAMP generation, contribute to the pathogenesis of dilated cardiomyopathy and the extent to which they constitute a beneficial compensatory response. Studies in animals involving overexpression and ablation of proteins or peptides involved in cAMP-mediated signalling have yielded disparate results that are difficult to reconcile with a simple hypothesis. Our ability to understand these differences is limited by the lack of information on how these different genetic manipulations affect the phosphorylation of individual substrates of protein kinase A (PKA) through which cAMP signals are transduced. This is important in view of evidence that the phosphorylation of individual PK-A substrates can be regulated selectively in different intracellular compartments, and that the phosphorylation of some PK-A substrates is increased in dilated cardiomyopathy while the phosphorylation of others is reduced. Approaches that quantify changes in the phosphorylation of individual PK-A substrates in models of dilated cardiomyopathy will provide information that may allow a better understanding of the pathogenesis of the syndrome and a more rational approach to its treatment. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:450 / 459
页数:10
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