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AMPK inhibits cardiac hypertrophy by promoting autophagy via mTORC1

Yanh Li1, Cong Chen1, Fengj Yao1

  • 1Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.

Archives of Biochemistry and Biophysics
|July 11, 2014
PubMed

Insights

AMP-activated protein kinase (AMPK) activation inhibits cardiac hypertrophy by boosting autophagy. This pathway involves inhibiting mTORC1 signaling, offering a potential therapeutic target for heart conditions.

Area of Science:

  • Cardiovascular Biology
  • Cellular Signaling
  • Metabolic Regulation

Background:

  • Cardiac hypertrophy is a significant risk factor for heart failure.
  • Autophagy plays a crucial role in maintaining cardiac homeostasis.
  • AMP-activated protein kinase (AMPK) is a known regulator of autophagy.

Purpose of the Study:

  • To investigate the role of AMPK in regulating cardiac hypertrophy via autophagy.
  • To determine the specific signaling pathways involved in AMPK-mediated autophagy in the heart.

Main Methods:

  • Utilized a pressure overload mouse model of cardiac hypertrophy.
  • Administered AMPK activators (AICAR, metformin) and assessed cardiac function and autophagy markers.
  • Conducted in vitro studies using cardiomyocytes with adenoviral AMPK overexpression.
  • Analyzed downstream signaling pathways including mTORC1 and mTORC2.

Main Results:

  • Pressure overload decreased cardiac autophagy; AMPK activators reversed hypertrophy and increased autophagy.
  • AMPK activation enhanced autophagosome formation with preserved lysosomal function.
  • In vitro, AMPK activation blunted cardiomyocyte hypertrophy and increased autophagy.
  • AMPK inhibited mTORC1 signaling (reduced 4EBP1/p70S6K phosphorylation) but not mTORC2 (AKT unaffected).

Conclusions:

  • AMPK activation inhibits cardiac hypertrophy by stimulating autophagy.
  • This effect is mediated through the inhibition of the mTORC1 signaling pathway.
  • Targeting the AMPK-autophagy-mTORC1 axis presents a potential therapeutic strategy for cardiac hypertrophy.

Keywords:
AMPKAutophagyCardiac hypertrophymTORC1

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