Omaveloxolone ameliorates isoproterenol-induced pathological cardiac hypertrophy in mice

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcriptional regulator that plays a protective role against various cardiovascular diseases. Omaveloxolone is a newly discovered potent activator of Nrf2 that has a variety of cytoprotective functions. However, the potential role of omaveloxolone in the process of pathological cardiac hypertrophy and heart failure are still unknown. In this study, an isoproterenol (ISO)-induced pathological cardiac hypertrophy model was established to investigate the protective effect of omaveloxolone in vivo and in vitro. Our study first confirmed that omaveloxolone administration improved ISO-induced pathological cardiac hypertrophy in mice and neonatal cardiomyocytes. Omaveloxolone administration also diminished ISO-induced cardiac oxidative stress, inflammation and cardiomyocyte apoptosis. In addition, omaveloxolone administration activated the Nrf2 signaling pathway, and Nrf2 knockdown almost completely abolished the cardioprotective effect of omaveloxolone, indicated that the cardioprotective effect of omaveloxolone was directly related to the activation of the Nrf2 signaling. In summary, our study identified that omaveloxolone may be a promising therapeutic agent to mitigate pathological cardiac hypertrophy.

Keywords:

• Omaveloxolone
• nuclear factor erythroid 2-related factor 2
• isoproterenol
• cardiac remodeling

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of Hubei province (2022CFC027), the Fundamental Research Funds for the Central Universities (2042023kf0042), and the Opening Foundation of Hubei Key Laboratory (2021KFY034)