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

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.