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

Humans Sodium-Glucose Transporter 2 Inhibitors / therapeutic use Heart Failure / metabolism Middle Aged Male Female Pericardium / metabolism Adipose Tissue / drug effects Treatment Outcome Inflammation Mediators / metabolism Severity of Illness Index Stroke Volume / drug effects Anti-Inflammatory Agents / therapeutic use Ventricular Function, Left / drug effects Diabetes Mellitus, Type 2 / drug therapy Metabolomics Biomarkers / blood Epicardial Adipose Tissue

Adipose tissue Ether lipids Heart failure Inflammation Sodium-glucose cotransporter 2 inhibitors

Journal

Cardiovascular diabetology

ISSN: 1475-2840

Titre abrégé: Cardiovasc Diabetol

Pays: England

ID NLM: 101147637

Informations de publication

Date de publication:
28 Jun 2024

Historique:

received: 03 03 2024

accepted: 05 06 2024

medline: 29 6 2024

pubmed: 29 6 2024

entrez: 29 6 2024

Statut: epublish

Résumé

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. 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/m 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. 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.

Sections du résumé

BACKGROUND BACKGROUND

METHODS 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/m

RESULTS 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 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.

Identifiants

DOI: 10.1186/s12933-024-02298-9 PMID: 38943140

pubmed: 38943140

doi: 10.1186/s12933-024-02298-9

pii: 10.1186/s12933-024-02298-9

doi:

Substances chimiques

Sodium-Glucose Transporter 2 Inhibitors 0

Inflammation Mediators 0

Anti-Inflammatory Agents 0

Biomarkers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

223

Subventions

Organisme : Ministerstvo Zdravotnictví Ceské Republiky

ID : NV19-02-00118

Organisme : National Institute for Research of Metabolic and Cardiovascular Diseases

ID : Programme EXCELES, ID Project No. LX22NPO5104 - Funded by the European Union- Next Generation EU

Organisme : CZ - DRO (Institute for Clinical and Experimental Medicine- IKEM)

ID : IN 00023001

Informations de copyright

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