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http://purl.uniprot.org/citations/15939815http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15939815http://www.w3.org/2000/01/rdf-schema#comment"

Background

Although disruption of guanylyl cyclase (GC) A, a natriuretic peptide receptor, induces cardiac hypertrophy and fibrosis, the molecular mechanism underlying these effects are not well understood. In this study, we examined the role of calcineurin, a calcium-dependent phosphatase, in cardiac remodeling in GCA-knockout (GCA-KO) mice.

Methods and results

At 14 weeks of age, calcineurin activity, nuclear translocation of nuclear factor of activated T cells c3 (NFATc3), and modulatory calcineurin-interacting protein 1 (MCIP1) gene expressions were increased in the hearts of GCA-KO mice compared with wild-type (WT) mice. Blockade of calcineurin activation by FK506 (6 mg/kg body weight administered subcutaneously once a day from 10 to 14 weeks of age) significantly decreased the heart-to-body weight ratio, cardiomyocyte size, and collagen volume fraction in GCA-KO mice, whereas FK506 did not affect these parameters in WT mice. Overexpression of atrial and brain natriuretic peptides, collagen, and fibronectin mRNAs in GCA-KO mice was also attenuated by FK506. Electrophoretic mobility shift assays demonstrated that GATA4 DNA-binding activity was increased in GCA-KO mice, and this increase was inhibited by calcineurin blockade. In neonatal cultured cardiac myocytes, inhibition of GCA by HS142-1 (100 microg/mL) increased basal and phenylephrine (10(-6) mol/L)-stimulated calcineurin activity, nuclear translocation of NFATc3, and MCIP1 mRNA expression. In contrast, activation of GCA by atrial natriuretic peptide (10(-6) mol/L) inhibited phenylephrine (10(-6) mol/L)-stimulated nuclear translocation of NFATc3.

Conclusions

These results suggest that activation of cardiac GCA by locally secreted natriuretic peptides protects the heart from excessive cardiac remodeling by inhibiting the calcineurin-NFAT pathway."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.104.510594"xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Horio T."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Mori K."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Kawano Y."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Nakao K."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Kangawa K."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Kohno M."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Garbers D.L."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Kishimoto I."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Tokudome T."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/author"Soeki T."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/pages"3095-3104"xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/title"Calcineurin-nuclear factor of activated T cells pathway-dependent cardiac remodeling in mice deficient in guanylyl cyclase A, a receptor for atrial and brain natriuretic peptides."xsd:string
http://purl.uniprot.org/citations/15939815http://purl.uniprot.org/core/volume"111"xsd:string
http://purl.uniprot.org/citations/15939815http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15939815
http://purl.uniprot.org/citations/15939815http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15939815
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