Anti-inflammatory and antioxidant effects of SGLT-2 inhibitors in epicardial adipose tissue of subjects with severe heart failure

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F23%3A00084387" target="_blank" >RIV/00023001:_____/23:00084387 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Anti-inflammatory and antioxidant effects of SGLT-2 inhibitors in epicardial adipose tissue of subjects with severe heart failure

Popis výsledku v původním jazyce

Background and aims: The exact mechanisms behind cardioprotective efects of SGLT-2 inhibitors (SGLT-2i) are still not fullyunderstood. Using complex transcriptomic, metabolomic and immunochemical methods we analysed epicardial (EAT) and subcutaneous(SAT) adipose tissue of patients with severe heart failure treated withSGLT-2i in order to identify possible cardioprotective pathways.Materials and methods: Twenty six subjects with severe heart failurewith reduced ejection fraction (NYHA III-IV) treated with SGLT-2i(18 with type 2 diabetes mellitus - T2DM) and 26 age-, BMI- and leftventricular ejection fraction-matched control subjects (8 with T2DM)scheduled for heart transplantation or mechanical support implantationwere included into the study. The complex analysis of EAT and SATincluded liquid chromatography in combination with mass spectrometry for metabolomics, RT-qPCR for transcriptomics and fow cytometryand immunochemistry for detection of immune cells and mitochondria.Results: Compared with controls, EAT of SGLT-2i subjects showedmarked reduction in macrophage infltration along with a decreasein Th1 and Th2 cells and mRNA levels of macrophage markerADGRE1. This was not the case for SAT, where only reduced mRNAlevels of inflammatory markers including IL6 and MCP1 weredetected. Moreover, mitochondrial staining revealed improvementof mitochondria morphology in EAT of SGLT-2i group accompanied by decreased oxidative stress. Finally, enhanced enrichment ofether lipids with oleic acid noted on metabolomic analysis suggestsreduced disposition to ferroptosis (iron-dependent lipid peroxidation-regulated cell death) further contributing to decreased oxidativestress in EAT of SGLT-2i subjects.Conclusion: SGLT-2i treatment is associated with reduced infammation and oxidative stress in epicardial adipose tissue, which couldat least partially explain their cardioprotective efects.

Název v anglickém jazyce

Anti-inflammatory and antioxidant effects of SGLT-2 inhibitors in epicardial adipose tissue of subjects with severe heart failure

Popis výsledku anglicky

Background and aims: The exact mechanisms behind cardioprotective efects of SGLT-2 inhibitors (SGLT-2i) are still not fullyunderstood. Using complex transcriptomic, metabolomic and immunochemical methods we analysed epicardial (EAT) and subcutaneous(SAT) adipose tissue of patients with severe heart failure treated withSGLT-2i in order to identify possible cardioprotective pathways.Materials and methods: Twenty six subjects with severe heart failurewith reduced ejection fraction (NYHA III-IV) treated with SGLT-2i(18 with type 2 diabetes mellitus - T2DM) and 26 age-, BMI- and leftventricular ejection fraction-matched control subjects (8 with T2DM)scheduled for heart transplantation or mechanical support implantationwere included into the study. The complex analysis of EAT and SATincluded liquid chromatography in combination with mass spectrometry for metabolomics, RT-qPCR for transcriptomics and fow cytometryand immunochemistry for detection of immune cells and mitochondria.Results: Compared with controls, EAT of SGLT-2i subjects showedmarked reduction in macrophage infltration along with a decreasein Th1 and Th2 cells and mRNA levels of macrophage markerADGRE1. This was not the case for SAT, where only reduced mRNAlevels of inflammatory markers including IL6 and MCP1 weredetected. Moreover, mitochondrial staining revealed improvementof mitochondria morphology in EAT of SGLT-2i group accompanied by decreased oxidative stress. Finally, enhanced enrichment ofether lipids with oleic acid noted on metabolomic analysis suggestsreduced disposition to ferroptosis (iron-dependent lipid peroxidation-regulated cell death) further contributing to decreased oxidativestress in EAT of SGLT-2i subjects.Conclusion: SGLT-2i treatment is associated with reduced infammation and oxidative stress in epicardial adipose tissue, which couldat least partially explain their cardioprotective efects.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

<a href="/cs/project/LX22NPO5104" target="_blank" >LX22NPO5104: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů