Dapagliflozin protects against dilated cardiomyopathy progression by targeting NLRP3 inflammasome activation

Naunyn Schmiedebergs Arch Pharmacol. 2023 Jul;396(7):1461-1470. doi: 10.1007/s00210-023-02409-5. Epub 2023 Feb 7.

Abstract

Dilated cardiomyopathy (DCM) is the major cause of heart failure and has a poor prognosis. The accumulating evidence points to an essential role of the inflammatory component in the process of DCM. Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are widely used to treat heart failure patients due to their cardiac benefits. However, their role in DCM remains unclear. We used the doxorubicin (Dox)-induced DCM model for our study. The SGLT2 inhibitor dapagliflozin (Dapa) improved cardiac function in mice treated with doxorubicin and attenuated the activation of the nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome pathway and the expression of inflammatory factors. In addition, dapagliflozin suppresses NLRP3 activation by decreasing p38-dependent toll-like receptor 4 (TLR4) expression. In our study, dagliflozin improves cardiac function in DCM by inhibiting the activity of the NLRP3 inflammasome.

Keywords: Dilated cardiomyopathy; Inflammation; NLRP3 inflammasome; SGLT2 inhibitors; TLR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathy, Dilated* / complications
  • Cardiomyopathy, Dilated* / drug therapy
  • Diabetic Cardiomyopathies*
  • Heart Failure*
  • Inflammasomes / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • dapagliflozin