Reviews in Cardiovascular Medicine · Oct 20, 2026

Dapagliflozin Attenuates Post-Infarction Myocardial Fibrosis Associated With the Inhibition of NLRP3-Dependent Inflammation

By Han X, Zhang J, Guo P et al.

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have attracted considerable attention owing to their unexpected cardioprotective benefits in addition to glycemic control. Indeed, these inhibitors have been reported to exert anti-fibrotic effects and ameliorate NACHT, leucine-rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3)-dependent inflammation. However, whether SGLT2 inhibitors (SGLT2is) attenuate post-infarction myocardial fibrosis by suppressing NLRP3-dependent signaling remains unclear. Thus, this study aimed to investigate the mechanisms through which the SGLT2is dapagliflozin (DAPA) mitigates post-infarction myocardial fibrosis, with particular emphasis on the modulation of NLRP3-dependent signaling. Methods: Male Sprague-Dawley rats were used to establish a myocardial infarction (MI) model via left coronary artery ligation and were treated with DAPA (1 mg/kg/day). Cardiac magnetic resonance imaging was performed to evaluate cardiac function and remodeling. Serial 18F-fibroblast activation protein inhibitor-74 (18F-FAPI-74) positron emission tomography (PET) was used to track temporal changes in cardiac fibroblast (CF) activation. Myocardial fibrosis and NLRP3-dependent signaling were assessed ex vivo. The effects of DAPA on NLRP3-dependent signaling, fibroblast proliferation, phenotypic transition, and collagen synthesis were determined in vitro using cardiac fibroblasts (CFs) stimulated with lipopolysaccharide. Results: Compared with untreated MI rats, MI rats treated with DAPA exhibited significantly lower left ventricular (LV) end-systolic volume, LV end-diastolic volume, and LV mass, along with improved LV ejection fraction (57.6 ± 2.4% vs. 54.4 ± 2.1% in the MI group; p = 0.011). LV fibrosis was reduced in DAPA-treated MI rats (20.1 ± 1.9% vs. 31.1 ± 4.0% in the MI group; p = 0.0026), and fibrosis markers were significantly downregulated. In vivo 18F-FAPI-74 PET revealed that DAPA suppressed CF activation, as demonstrated by significantly reduced 18F-FAPI-74 uptake in the infarcted region. In infarcted cardiac tissue, DAPA inhibited the expression of the NLRP3 inflammasome, interleukin-1 beta (IL-1β), and interleukin-18 (IL-18). CF experiments performed in vitro showed that DAPA inhibited the nuclear factor kappa B (NF-κB)/NLRP3 pathway and attenuated CF proliferation, phenotypic transition, and collagen synthesis. Conclusions: By suppressing CF activation, DAPA improved myocardial fibrosis, adverse LV remodeling, and cardiac function post-MI, in association with inhibition of the NF-κB/NLRP3 pathway. 18F-FAPI-74 PET enabled non-invasive visualization of the anti-fibrotic effects of DAPA post-MI and may serve as a tool to monitor anti-fibrotic treatment efficacy after MI.

doi.org/10.31083/rcm51179 Open access PubMed 42985526 Interventions