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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...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
Grantová podpora
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
od 2002-12-01
BioMedCentral Open Access
od 2002
Directory of Open Access Journals
od 2002
Free Medical Journals
od 2002
PubMed Central
od 2002
Europe PubMed Central
od 2002
ProQuest Central
od 2009-01-01
Open Access Digital Library
od 2002-01-01
Open Access Digital Library
od 2002-01-01
Open Access Digital Library
od 2002-04-01
Medline Complete (EBSCOhost)
od 2002-04-08
Health & Medicine (ProQuest)
od 2009-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2002
Springer Nature OA/Free Journals
od 2002-12-01
- MeSH
- antiflogistika terapeutické užití farmakologie MeSH
- biologické markery krev MeSH
- diabetes mellitus 2. typu farmakoterapie metabolismus diagnóza MeSH
- epikardiální adipózní tkáň MeSH
- funkce levé komory srdeční účinky léků MeSH
- glifloziny * terapeutické užití farmakologie škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu * metabolismus MeSH
- metabolomika MeSH
- perikard * metabolismus účinky léků MeSH
- srdeční selhání * metabolismus patofyziologie farmakoterapie MeSH
- stupeň závažnosti nemoci * MeSH
- tepový objem účinky léků MeSH
- tuková tkáň * účinky léků metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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
Citace poskytuje Crossref.org
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- $a 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.
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