A novel mechanism of protection against isoproterenol-induced cardiac inflammation via regulation of the SIRT1/NRF2 signaling pathway with a natural SIRT1 agonist

Eur J Pharmacol. 2020 Nov 5:886:173398. doi: 10.1016/j.ejphar.2020.173398. Epub 2020 Aug 4.

Abstract

Stress-induced cardiomyopathy (SIC) is associated with high mortality rates, potentially due to a lack of available therapies. To facilitate the identification of therapeutic targets for SIC, we explored the detailed mechanisms of disease onset and progression using a mouse model. Over-activation of the β-adrenergic receptor (β-AR) upon stress leads to inflammasome activation, cytokine cascades, macrophage infiltration, and pathological cardiac remodeling in mice, mimicking SIC. However, the detailed mechanisms by which acute β-AR stimulation induces cardiac inflammation remain elusive. We found that resveratrol (RSV) could attenuate isoproterenol-induced cardiac inflammation in mice, suggesting that RSV might be a promising therapeutic option in SIC. Mechanistically, we revealed that the SIRT1/NRF2 signaling pathway is the bona fide target of RSV and plays a significant role in the RSV-induced protective effect in cardiac inflammation.

Keywords: Cardiac inflammation; NRF2; Resveratrol; SIRT1; Stress-induced cardiomyopathy.

MeSH terms

  • Adrenergic beta-Agonists*
  • Animals
  • Antioxidants / therapeutic use
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cytokine Release Syndrome / chemically induced
  • Cytokine Release Syndrome / prevention & control
  • Inflammasomes / drug effects
  • Isoproterenol*
  • Macrophage Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocarditis / chemically induced*
  • Myocarditis / prevention & control*
  • NF-E2-Related Factor 2 / drug effects*
  • Resveratrol / therapeutic use
  • Signal Transduction / drug effects*
  • Sirtuin 1 / drug effects*

Substances

  • Adrenergic beta-Agonists
  • Antioxidants
  • Cardiotonic Agents
  • Inflammasomes
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Isoproterenol
  • Resveratrol