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SIRT1-mediated acute cardioprotection.

Sergiy M Nadtochiy1, Hongwei Yao, Michael W McBurney

  • 1Department of Anesthesiology, University of Rochester Medical Center, Rochester, New York 14642, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|August 23, 2011
PubMed
Summary

Silent Information Regulator of Transcription 1 (SIRT1) is crucial for acute cardioprotection during ischemic preconditioning (IPC). SIRT1

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Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Biochemistry

Background:

  • Silent Information Regulator of Transcription 1 (SIRT1) lysine deacetylase is known for long-term cardioprotection.
  • The role of SIRT1 in acute cardioprotection via short-term deacetylation is not well understood.

Purpose of the Study:

  • To investigate the role of SIRT1 in acute cardioprotection using the first window of ischemic preconditioning (IPC).
  • To elucidate the mechanisms of SIRT1-mediated deacetylation in short-term cardioprotective signaling.

Main Methods:

  • Utilized SIRT1-deficient (SIRT1(+/-)) and SIRT1-overexpressing (SIRT1(+++)) mice models.
  • Examined cytosolic lysine deacetylation/acetylation levels during IPC in wild-type and genetically modified hearts.
  • Assessed cardioprotection against ischemia-reperfusion injury.

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  • Investigated downstream targets including endothelial nitric oxide synthase phosphorylation, NF-κB, and autophagy.

    • Main Results:

    • Wild-type hearts showed cytosolic deacetylation during IPC, while SIRT1 inhibition led to overacetylation.
    • SIRT1(+/-) hearts lacked preconditioning effects and showed increased acetylation.
    • SIRT1(+++) hearts exhibited endogenous protection against ischemia-reperfusion injury with decreased acetylation, effects reversible by SIRT1 inhibition.
    • Potential downstream targets involved in SIRT1's acute cardioprotective role were identified.

    Conclusions:

    • SIRT1 is essential for acute cardioprotection mediated by ischemic preconditioning, acting on non-transcriptional targets.
    • SIRT1-dependent lysine deacetylation occurs during IPC and contributes to cardioprotective signaling pathways.
    • These findings highlight SIRT1's critical role in short-term cardiac protection mechanisms.