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http://purl.uniprot.org/citations/18056528http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18056528http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18056528http://www.w3.org/2000/01/rdf-schema#comment"

Background

Rad (Ras associated with diabetes) GTPase is the prototypic member of a subfamily of Ras-related small G proteins. The aim of the present study was to define whether Rad plays an important role in mediating cardiac hypertrophy.

Methods and results

We document for the first time that levels of Rad mRNA and protein were decreased significantly in human failing hearts (n=10) compared with normal hearts (n=3; P<0.01). Similarly, Rad expression was decreased significantly in cardiac hypertrophy induced by pressure overload and in cultured cardiomyocytes with hypertrophy induced by 10 micromol/L phenylephrine. Gain and loss of Rad function in cardiomyocytes significantly inhibited and increased phenylephrine-induced hypertrophy, respectively. In addition, activation of calcium-calmodulin-dependent kinase II (CaMKII), a strong inducer of cardiac hypertrophy, was significantly inhibited by Rad overexpression. Conversely, downregulation of CaMKIIdelta by RNA interference technology attenuated the phenylephrine-induced hypertrophic response in cardiomyocytes in which Rad was also knocked down. To further elucidate the potential role of Rad in vivo, we generated Rad-deficient mice and demonstrated that they were more susceptible to cardiac hypertrophy associated with increased CaMKII phosphorylation than wild-type littermate controls.

Conclusions

The present data document for the first time that Rad is a novel mediator that inhibits cardiac hypertrophy through the CaMKII pathway. The present study will have significant implications for understanding the mechanisms of cardiac hypertrophy and setting the basis for the development of new strategies for treatment of cardiac hypertrophy."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.107.707257"xsd:string
http://purl.uniprot.org/citations/18056528http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.107.707257"xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Chang L."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Chang L."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Kahn C.R."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Kahn C.R."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Sun Z."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Sun Z."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Yang Q."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Yang Q."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Tseng Y.-H."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Tseng Y.-H."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Zhu X."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Zhu X."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Cui T."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Cui T."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Bruning J.C."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Bruning J.C."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Chen Y.E."xsd:string
http://purl.uniprot.org/citations/18056528http://purl.uniprot.org/core/author"Chen Y.E."xsd:string
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