Short-term targeting of the circadian regulator REV-ERB with the agonist SR9009 promotes cardiac repair after ischaemia–reperfusion injury in mice, according to a new study. These cardioprotective effects are mediated by repression of inflammatory responses. Treatment with SR9009 for just 1 day after myocardial ischaemia–reperfusion in mice increased the transcriptional repressor activity of REV-ERB and reduced the mRNA levels of cytokines and the NLRP3 inflammasome. Treated mice had less recruitment of immune cells to the infarct, reduced infarct size, less adverse remodelling and were protected against heart failure development compared with untreated mice. By contrast, SR9009 treatment in mice with REV-ERB deficiency did not impart cardioprotective benefits. Further analyses showed that cardiac fibroblasts were the cellular targets contributing to these cardioprotective effects.
Reitz, C. J. et al. SR9009 administered for one day after myocardial ischemia-reperfusion prevents heart failure in mice by targeting the cardiac inflammasome. Commun. Biol. 2, 353 (2019)
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Fernández-Ruiz, I. Circadian regulators as a therapeutic target in MI. Nat Rev Cardiol 17, 6 (2020). https://doi.org/10.1038/s41569-019-0303-1