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Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2010 Mar 23; Vol. 107 (12), pp. 5646-51. Date of Electronic Publication: 2010 Mar 08. - Publication Year :
- 2010
-
Abstract
- 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 cGKIbeta rescue mice (betaRM) lacking cGKI specifically in cardiomyocytes (CMs). Infusion of ISO did not change the expression of cGKI in the hearts of CTR mice or betaRM but raised the heart weight by approximately 20% in both. An identical hypertrophic growth response was measured in CMs from CTR mice and betaRM and in isolated adult CMs cultured with or without 1 muM 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 betaRM 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.
- Subjects :
- Animals
Base Sequence
Cardiomegaly genetics
Cardiomegaly pathology
Cells, Cultured
Cyclic GMP-Dependent Protein Kinase Type I
Cyclic GMP-Dependent Protein Kinases genetics
DNA Primers genetics
Gene Expression
Isoproterenol pharmacology
Mice
Mice, Knockout
Models, Cardiovascular
Myocytes, Cardiac pathology
Myocytes, Smooth Muscle enzymology
RNA, Messenger genetics
RNA, Messenger metabolism
Signal Transduction
Cardiomegaly enzymology
Cardiomegaly etiology
Cyclic GMP-Dependent Protein Kinases deficiency
Myocytes, Cardiac enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 107
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 20212138
- Full Text :
- https://doi.org/10.1073/pnas.1001360107