Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes
Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes
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DOI：
10.1073/pnas.1001360107
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发表时间：
2010-03-23
影响因子：
11.1
通讯作者：
Hofmann, Franz
中科院分区：
文献类型：
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作者：
Lukowski, Robert;Rybalkin, Sergei D.;Hofmann, Franz
已表明cGMP激酶I（cGKI）抑制心脏肥大。我们比较了异丙肾上腺素（ISO）和横主动脉缩窄（TAC）对WT [对照（CTR）]小鼠、总cGKI-KO小鼠和心肌细胞（CM）中缺乏cGKI的cGKI β拯救小鼠（β RM）肥大的影响。ISO的输注没有改变CTR小鼠或β RM心脏中cGKI的表达，但两者的心脏重量都增加了20%。在CTR小鼠和β RM的CM中以及在用或不用1 μ M ISO培养的分离的成人CM中测量了相同的肥大生长反应。在这两种基因型中，ISO输注诱导肥大相关心脏基因表达的相似变化，以及血清心钠素和总心脏cGMP的显著升高。在4至6周龄的常规cGKI-KO和CTR小鼠中，通过7天ISO输注未获得心脏肥大的差异。此外，TAC诱导的CTR小鼠和β RM的肥大没有不同，并且不会导致肥厚心脏或CM中cGMP水解磷酸二酯酶活性的变化。这些结果强烈表明，心肌细胞cGKI不影响压力超负荷或慢性ISO输注诱导的心脏肥大的发展。
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 similar to 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 mu 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.