Frontiers in Pharmacology (Mar 2021)

Antifibrotic Effect of a Novel Selective 11β-HSD2 Inhibitor (WZ51) in a rat Model of Myocardial Fibrosis

  • Fei Zhuang,
  • Fei Zhuang,
  • Fei Zhuang,
  • Qin Ge,
  • Jianchang Qian,
  • Zhe Wang,
  • Yaoyao Dong,
  • Mengchun Chen,
  • Xiaodan Zhang,
  • Wei Sun

DOI
https://doi.org/10.3389/fphar.2021.629818
Journal volume & issue
Vol. 12

Abstract

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Myocardial fibrosis (MF) is one of the leading causes of end-stage heart disease. Many studies have confirmed that inflammation caused by aldosterone may play an important role in the process of MF. A selective 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme inhibitor can reduce the inactivation of cortisol, allowing cortisol to compete for mineralocorticoid receptors. This study investigated the protective effect of a novel selective 11βHSD2 inhibitor (WZ51) on MF and described its underlying mechanism. The administration of WZ51 in rats with MF significantly alleviated myocardial injury, accompanied by a decrease in lactate dehydrogenase and the creatine kinase myocardial band. Furthermore, WZ51 significantly inhibited the development of MF and increased the protein level of 11β-HSD2. The results of this study demonstrate that 11β-HSD2 plays an important pathological role in MF. Thus, WZ51 may be a potential therapeutic agent for the treatment of this condition.

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