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Sodium-glucose cotransporter 2 inhibitors induce anti-inflammatory and anti-ferroptotic shift in epicardial adipose tissue of subjects with severe heart failure
BJ. Kasperova, M. Mraz, P. Svoboda, D. Hlavacek, H. Kratochvilova, I. Modos, N. Vrzackova, P. Ivak, P. Janovska, T. Kobets, J. Mahrik, M. Riecan, L. Steiner Mrazova, V. Stranecky, I. Netuka, T. Cajka, O. Kuda, V. Melenovsky, S. Stemberkova...
Language English Country England, Great Britain
Document type Journal Article
Grant support
NV19-02-00118
Ministerstvo Zdravotnictví Ceské Republiky
Programme EXCELES, ID Project No. LX22NPO5104 - Funded by the European Union- Next Generation EU
National Institute for Research of Metabolic and Cardiovascular Diseases
IN 00023001
CZ - DRO (Institute for Clinical and Experimental Medicine- IKEM)
NLK
BioMedCentral
from 2002-12-01
BioMedCentral Open Access
from 2002
Directory of Open Access Journals
from 2002
Free Medical Journals
from 2002
PubMed Central
from 2002
Europe PubMed Central
from 2002
ProQuest Central
from 2009-01-01
Open Access Digital Library
from 2002-01-01
Open Access Digital Library
from 2002-01-01
Open Access Digital Library
from 2002-04-01
Medline Complete (EBSCOhost)
from 2002-04-08
Health & Medicine (ProQuest)
from 2009-01-01
ROAD: Directory of Open Access Scholarly Resources
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Springer Nature OA/Free Journals
from 2002-12-01
- MeSH
- Anti-Inflammatory Agents therapeutic use pharmacology MeSH
- Biomarkers blood MeSH
- Diabetes Mellitus, Type 2 drug therapy metabolism diagnosis MeSH
- Epicardial Adipose Tissue MeSH
- Ventricular Function, Left drug effects MeSH
- Sodium-Glucose Transporter 2 Inhibitors * therapeutic use pharmacology adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Inflammation Mediators * metabolism MeSH
- Metabolomics MeSH
- Pericardium * metabolism drug effects MeSH
- Heart Failure * metabolism physiopathology drug therapy MeSH
- Severity of Illness Index * MeSH
- Stroke Volume drug effects MeSH
- Adipose Tissue * drug effects metabolism MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Sodium-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. METHODS: 26 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. RESULTS: SGLT-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. CONCLUSIONS: Our 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.
1st Faculty of Medicine Charles University Prague Katerinska 1660 32 121 08 Prague Czech Republic
3rd Faculty of Medicine Charles University Prague Ruska 87 100 00 Prague Czech Republic
References provided by Crossref.org
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