National Institute for Research of Metabolic and Cardiovascular Diseases
Published January 1, 2024 | Version v1
Journal article Open

Sodium-glucose cotransporter 2 inhibitors induce anti-inflammatory and anti-ferroptotic shift in epicardial adipose tissue of subjects with severe heart failure

Creators

  • 1. Institut klinicke a experimentalni mediciny
  • 2. Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technicka 5, 166 28, Prague, Czech Republic
  • 3. Department of Adipose Tissue Biology, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 00, Prague, Czech Republic
  • 4. Department of Metabolomics, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 00, Prague, Czech Republic
  • 5. Department of Metabolism of Bioactive Lipids, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 00, Prague, Czech Republic
  • 6. Research Unit for Rare Diseases, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Ke Karlovu 455/2, 128 08, Prague, Czech Republic

Description

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure.Methods26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 +/- 2.1 vs. 55.3 +/- 2.1 years, n.s.), body mass index (27.8 +/- 0.9 vs. 28.8 +/- 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 +/- 0.5 vs. 23.2 +/- 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed.ResultsSGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects.ConclusionsOur results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.

Notes

This work was supported by a grant from the Czech Ministry of Health (NV19-02-00118 to M.M.), by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU and by CZ—DRO (“Institute for Clinical and Experimental Medicine—IKEM, IN 00023001”) to M.H. B.J.K. was supported by the Grant Agency of Charles University (GA UK 407822).

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38943140 (PMID)
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1475-2840 (ISSN)
1475-2840 (ISSN)
References
10.1186/s12933-024-02298-9 (DOI)