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标题：Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes
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作者：Robert Lukowski ; Sergei D. Rybalkin ; Florian Loga 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：12
页码：5646-5651
DOI：10.1073/pnas.1001360107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：It has been suggested that cGMP kinase I (cGKI) dampens cardiac hypertrophy. We have compared the effect of isoproterenol (ISO) and transverse aortic constriction (TAC) on hypertrophy in WT [control (CTR)] mice, total cGKI-KO mice, and cGKI{beta} rescue mice ({beta}RM) lacking cGKI specifically in cardiomyocytes (CMs). Infusion of ISO did not change the expression of cGKI in the hearts of CTR mice or {beta}RM but raised the heart weight by [~]20% in both. An identical hypertrophic growth response was measured in CMs from CTR mice and {beta}RM and in isolated adult CMs cultured with or without 1 {micro}M ISO. In both genotypes, ISO infusion induced similar changes in the expression of hypertrophy-associated cardiac genes and significant elevation of serum atrial natriuretic peptide and total cardiac cGMP. No differences in cardiac hypertrophy were obtained by 7-day ISO infusion in 4- to 6-week-old conventional cGKI-KO and CTR mice. Furthermore, TAC-induced hypertrophy of CTR mice and {beta}RM was not different and did not result in changes of the cGMP-hydrolyzing phosphodiesterase activities in hypertropic hearts or CMs. These results strongly suggest that cardiac myocyte cGKI does not affect the development of heart hypertrophy induced by pressure overload or chronic ISO infusion.
关键词：cyclic nucleotides ; phosphodiesterase ; phosphorylation ; transverse aortic constriction ; sildenafil