Dapagliflozin Attenuates Post-Infarction Myocardial Fibrosis Associated With the Inhibition of NLRP3-Dependent Inflammation
5 affiliations
- 1Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, 030000 Taiyuan, Shanxi, China
- 2Department of Nuclear Medicine, First Hospital of Shanxi Medical University, 030000 Taiyuan, Shanxi, China
- 3Department of Cardiology, First Hospital of Shanxi Medical University, 030000 Taiyuan, Shanxi, China
- 4Department of Radiology, First Hospital of Shanxi Medical University, 030000 Taiyuan, Shanxi, China
- 5Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Shanxi Medical University, 030000 Taiyuan, Shanxi, China
Abstract
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.
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BibTeX
@article{han2026dapagliflozin,
title = {{Dapagliflozin Attenuates Post-Infarction Myocardial Fibrosis Associated With the Inhibition of NLRP3-Dependent Inflammation}},
author = {Xiao Han and Jun Zhang and Pingchang Guo and Junshun Chang and Bing Liu and Xin Diao and Ping Wu and Sheng He and Hua Wei and Wenjuan Dai and Yu Hong and Yuwen Chen and Li Li and Ruonan Wang and Zhifang Wu and Sijin Li},
journal = {Reviews in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.31083/rcm51179},
url = {https://doi.org/10.31083/rcm51179},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dapagliflozin Attenuates Post-Infarction Myocardial Fibrosis Associated With the Inhibition of NLRP3-Dependent Inflammation
AU - Xiao Han
AU - Jun Zhang
AU - Pingchang Guo
AU - Junshun Chang
AU - Bing Liu
AU - Xin Diao
AU - Ping Wu
AU - Sheng He
AU - Hua Wei
AU - Wenjuan Dai
AU - Yu Hong
AU - Yuwen Chen
AU - Li Li
AU - Ruonan Wang
AU - Zhifang Wu
AU - Sijin Li
PY - 2026
DA - 2026/10/20
JO - Reviews in Cardiovascular Medicine
DO - 10.31083/rcm51179
UR - https://doi.org/10.31083/rcm51179
AB - 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.
SN - 1530-6550
SN - 2153-8174
ER -