RGD Reference Report - mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy. - Rat Genome Database

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mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy.

Authors: Song, X  Kusakari, Y  Xiao, CY  Kinsella, SD  Rosenberg, MA  Scherrer-Crosbie, M  Hara, K  Rosenzweig, A  Matsui, T 
Citation: Song X, etal., Am J Physiol Cell Physiol. 2010 Dec;299(6):C1256-66. doi: 10.1152/ajpcell.00338.2010. Epub 2010 Sep 22.
RGD ID: 10003169
Pubmed: PMID:20861467   (View Abstract at PubMed)
PMCID: PMC3006320   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpcell.00338.2010   (Journal Full-text)

Previous studies have suggested that inhibition of the mammalian target of rapamycin (mTOR) by rapamycin suppresses myocardial hypertrophy. However, the role of mTOR in the progression of cardiac dysfunction in pathological hypertrophy has not been fully defined. Interestingly, recent reports indicate that the inflammatory response, which plays an important role in the development of heart failure, is enhanced by rapamycin under certain conditions. Our aim in this study was to determine the influence of mTOR on pathological hypertrophy and to assess whether cardiac mTOR regulates the inflammatory response. We generated transgenic mice with cardiac-specific overexpression of wild-type mTOR (mTOR-Tg). mTOR-Tg mice were protected against cardiac dysfunction following left ventricular pressure overload induced by transverse aortic constriction (TAC) (P < 0.01) and had significantly less interstitial fibrosis compared with littermate controls (WT) at 4 wk post-TAC (P < 0.01). In contrast, TAC caused cardiac dysfunction in WT. At 1 wk post-TAC, the proinflammatory cytokines interleukin (IL)-1beta and IL-6 were significantly increased in WT mice but not in mTOR-Tg mice. To further characterize the effects of mTOR activation, we exposed HL-1 cardiomyocytes transfected with mTOR to lipopolysaccharide (LPS). mTOR overexpression suppressed LPS-induced secretion of IL-6 (P < 0.001), and the mTOR inhibitors rapamycin and PP242 abolished this inhibitory effect of mTOR. In addition, mTOR overexpression reduced NF-kappaB-regulated transcription in HL-1 cells. These data suggest that mTOR mitigates adverse outcomes of pressure overload and that this cardioprotective effect of mTOR is mediated by regulation of the inflammatory reaction.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOMtor (Rattus norvegicus)10003169; 10003169associated with Aortic Valve StenosisRGD 
Cardiomegaly  IMP 10003169associated with Aortic Valve StenosisRGD 
congestive heart failure  IEP 10003169mRNA and protein:increased expression:heartRGD 
congestive heart failure  ISOMTOR (Homo sapiens)10003169; 10003169mRNA and protein:increased expression:heartRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Mus musculus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Homo sapiens)
MTOR  (mechanistic target of rapamycin kinase)


Additional Information