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September 23, 2010AJP Cell PhysiologyOpen Access

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

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Key result

Cardiac-specific overexpression of mTOR protected mice against pressure overload-induced cardiac dysfunction and reduced interstitial fibrosis by approximately 60% compared to wild-type controls.

Why the study?

Does mTOR overexpression prevent cardiac dysfunction and attenuate the inflammatory response in pathological hypertrophy?

Population

Transgenic mice with cardiac-specific overexpression of wild-type mTOR and littermate controls subjected to…

Comparison

Cardiac-specific overexpression of wild-type… vs Littermate controls for in vivo; non-transfected…

Design

Preclinical

Follow-up

Up to 4 weeks post-TAC

Authors

XSXiaoxiao SongYKYoichiro KusakariCXChunyang Xiao

Discussion

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Member takes

Overview

No immediate clinical implications; leaves open mTOR modulation as a therapeutic target in human pressure-overload hypertrophy.

Structured PICO

Does mTOR overexpression prevent cardiac dysfunction and attenuate the inflammatory response in pathological hypertrophy?

P
Population
Transgenic mice with cardiac-specific overexpression of wild-type mTOR (mTOR-Tg) and littermate controls (WT) subjected to transverse aortic constriction (TAC); HL-1 cardiomyocytes exposed to lipopolysaccharide (LPS)
I
Intervention
Cardiac-specific overexpression of wild-type mTOR (in vivo) and mTOR transfection (in vitro)
C
Comparator
Littermate controls (WT) for in vivo; non-transfected or inhibitor-treated (rapamycin, PP242) cells for in vitro
O
Outcome
Cardiac dysfunction and interstitial fibrosis following left ventricular pressure overloadsurrogate

Main Result

p-value: p=<0.01

Cardiac-specific overexpression of mTOR protects against pressure overload-induced cardiac dysfunction and fibrosis by attenuating the inflammatory response.

Limitations

  • Small sample size for human tissue analysis
  • Findings primarily based on transgenic mouse and in vitro models which may not fully translate to human clinical outcomes

Cite This Study

Song et al. (2010) studied Pathological cardiac hypertrophy and heart failure (n=10). Cardiac-specific overexpression of wild-type mTOR vs. Wild-type littermates was evaluated on Interstitial fibrosis and cardiac dysfunction following transverse aortic constriction (p=<0.01). Cardiac-specific overexpression of mTOR protected mice against pressure overload-induced cardiac dysfunction and reduced interstitial fibrosis by approximately 60% compared to wild-type controls.

synapsesocial.com/papers/6a1c19cf00ee29383e9d7417https://doi.org/10.1152/ajpcell.00338.2010
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Rapamycin Attenuates Load-Induced Cardiac Hypertrophy in Mice2003 · 466 citations
  2. 2Role of interleukin‐6 in cardiomyocyte/cardiac fibroblast interactions during myocyte hypertrophy and fibroblast proliferation2005 · 115 citations
  3. 3Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells2008 · 215 citations
  4. 4Cardiac Restricted Overexpression of Kinase-dead Mammalian Target of Rapamycin (mTOR) Mutant Impairs the mTOR-mediated Signaling and Cardiac Function2008 · 65 citations
  5. 5Phenotypic Spectrum Caused by Transgenic Overexpression of Activated Akt in the Heart2002 · 438 citations