Cargando…

Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction

Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIR...

Descripción completa

Detalles Bibliográficos
Autores principales: Sardu, Celestino, D’Onofrio, Nunzia, Torella, Michele, Portoghese, Michele, Mureddu, Simone, Loreni, Francesco, Ferraraccio, Franca, Panarese, Iacopo, Trotta, Maria Consiglia, Gatta, Gianluca, Galdiero, Marilena, Sasso, Ferdinando Carlo, D’Amico, Michele, De Feo, Marisa, Balestrieri, Maria Luisa, Paolisso, Giuseppe, Marfella, Raffaele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389537/
https://www.ncbi.nlm.nih.gov/pubmed/34440108
http://dx.doi.org/10.3390/biomedicines9080904
_version_ 1783742881428668416
author Sardu, Celestino
D’Onofrio, Nunzia
Torella, Michele
Portoghese, Michele
Mureddu, Simone
Loreni, Francesco
Ferraraccio, Franca
Panarese, Iacopo
Trotta, Maria Consiglia
Gatta, Gianluca
Galdiero, Marilena
Sasso, Ferdinando Carlo
D’Amico, Michele
De Feo, Marisa
Balestrieri, Maria Luisa
Paolisso, Giuseppe
Marfella, Raffaele
author_facet Sardu, Celestino
D’Onofrio, Nunzia
Torella, Michele
Portoghese, Michele
Mureddu, Simone
Loreni, Francesco
Ferraraccio, Franca
Panarese, Iacopo
Trotta, Maria Consiglia
Gatta, Gianluca
Galdiero, Marilena
Sasso, Ferdinando Carlo
D’Amico, Michele
De Feo, Marisa
Balestrieri, Maria Luisa
Paolisso, Giuseppe
Marfella, Raffaele
author_sort Sardu, Celestino
collection PubMed
description Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIRT6) expression in PDM vs. normoglycemic (NG) patients undergoing coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). However, in the current study, we evaluated inflammatory markers, SGLT2, SIRT6, and leptin levels in pericoronary fat and, subsequently, 12-month prognosis comparing PDM to NG subjected to CABG for AMI. In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels. Methods: we studied AMI patients referred for CABG, divided into PDM and NG-patients. PDM patients were divided into never-metformin users and metformin users. Finally, we evaluated major adverse cardiac events (MACE) at a 12-month follow-up. Results: the MACE was 9.1% in all PDM and 3% in NG patients (p < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (p < 0.05). PDM showed higher inflammatory cytokines, 3-nitrotyrosine levels, SGLT2, and leptin content, and decreased SIRT6 protein levels in pericoronary fat compared to NG-patients (p < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Conclusions: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG.
format Online
Article
Text
id pubmed-8389537
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83895372021-08-27 Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction Sardu, Celestino D’Onofrio, Nunzia Torella, Michele Portoghese, Michele Mureddu, Simone Loreni, Francesco Ferraraccio, Franca Panarese, Iacopo Trotta, Maria Consiglia Gatta, Gianluca Galdiero, Marilena Sasso, Ferdinando Carlo D’Amico, Michele De Feo, Marisa Balestrieri, Maria Luisa Paolisso, Giuseppe Marfella, Raffaele Biomedicines Article Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIRT6) expression in PDM vs. normoglycemic (NG) patients undergoing coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). However, in the current study, we evaluated inflammatory markers, SGLT2, SIRT6, and leptin levels in pericoronary fat and, subsequently, 12-month prognosis comparing PDM to NG subjected to CABG for AMI. In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels. Methods: we studied AMI patients referred for CABG, divided into PDM and NG-patients. PDM patients were divided into never-metformin users and metformin users. Finally, we evaluated major adverse cardiac events (MACE) at a 12-month follow-up. Results: the MACE was 9.1% in all PDM and 3% in NG patients (p < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (p < 0.05). PDM showed higher inflammatory cytokines, 3-nitrotyrosine levels, SGLT2, and leptin content, and decreased SIRT6 protein levels in pericoronary fat compared to NG-patients (p < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Conclusions: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG. MDPI 2021-07-28 /pmc/articles/PMC8389537/ /pubmed/34440108 http://dx.doi.org/10.3390/biomedicines9080904 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sardu, Celestino
D’Onofrio, Nunzia
Torella, Michele
Portoghese, Michele
Mureddu, Simone
Loreni, Francesco
Ferraraccio, Franca
Panarese, Iacopo
Trotta, Maria Consiglia
Gatta, Gianluca
Galdiero, Marilena
Sasso, Ferdinando Carlo
D’Amico, Michele
De Feo, Marisa
Balestrieri, Maria Luisa
Paolisso, Giuseppe
Marfella, Raffaele
Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction
title Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction
title_full Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction
title_fullStr Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction
title_full_unstemmed Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction
title_short Metformin Therapy Effects on the Expression of Sodium-Glucose Cotransporter 2, Leptin, and SIRT6 Levels in Pericoronary Fat Excised from Pre-Diabetic Patients with Acute Myocardial Infarction
title_sort metformin therapy effects on the expression of sodium-glucose cotransporter 2, leptin, and sirt6 levels in pericoronary fat excised from pre-diabetic patients with acute myocardial infarction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389537/
https://www.ncbi.nlm.nih.gov/pubmed/34440108
http://dx.doi.org/10.3390/biomedicines9080904
work_keys_str_mv AT sarducelestino metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT donofrionunzia metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT torellamichele metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT portoghesemichele metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT mureddusimone metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT lorenifrancesco metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT ferraracciofranca metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT panareseiacopo metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT trottamariaconsiglia metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT gattagianluca metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT galdieromarilena metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT sassoferdinandocarlo metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT damicomichele metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT defeomarisa metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT balestrierimarialuisa metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT paolissogiuseppe metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction
AT marfellaraffaele metformintherapyeffectsontheexpressionofsodiumglucosecotransporter2leptinandsirt6levelsinpericoronaryfatexcisedfromprediabeticpatientswithacutemyocardialinfarction