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...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/8/904 |
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| author | Celestino Sardu Nunzia D’Onofrio Michele Torella Michele Portoghese Simone Mureddu Francesco Loreni Franca Ferraraccio Iacopo Panarese Maria Consiglia Trotta Gianluca Gatta Marilena Galdiero Ferdinando Carlo Sasso Michele D’Amico Marisa De Feo Maria Luisa Balestrieri Giuseppe Paolisso Raffaele Marfella |
| author_facet | Celestino Sardu Nunzia D’Onofrio Michele Torella Michele Portoghese Simone Mureddu Francesco Loreni Franca Ferraraccio Iacopo Panarese Maria Consiglia Trotta Gianluca Gatta Marilena Galdiero Ferdinando Carlo Sasso Michele D’Amico Marisa De Feo Maria Luisa Balestrieri Giuseppe Paolisso Raffaele Marfella |
| author_sort | Celestino Sardu |
| collection | DOAJ |
| 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 (<i>p</i> < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (<i>p</i> < 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 (<i>p</i> < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (<i>p</i> < 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. |
| first_indexed | 2024-03-10T08:59:09Z |
| format | Article |
| id | doaj.art-206237a153f846d7971404dff3be6eb5 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T08:59:09Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-206237a153f846d7971404dff3be6eb52023-11-22T06:51:46ZengMDPI AGBiomedicines2227-90592021-07-019890410.3390/biomedicines9080904Metformin 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 InfarctionCelestino Sardu0Nunzia D’Onofrio1Michele Torella2Michele Portoghese3Simone Mureddu4Francesco Loreni5Franca Ferraraccio6Iacopo Panarese7Maria Consiglia Trotta8Gianluca Gatta9Marilena Galdiero10Ferdinando Carlo Sasso11Michele D’Amico12Marisa De Feo13Maria Luisa Balestrieri14Giuseppe Paolisso15Raffaele Marfella16Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Cardiac Surgery, Santissima Annunziata Hospital, 07100 Sassari, ItalyDepartment of Cardiac Surgery, Santissima Annunziata Hospital, 07100 Sassari, ItalyDepartment of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyDepartment of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyBackground 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 (<i>p</i> < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (<i>p</i> < 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 (<i>p</i> < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (<i>p</i> < 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.https://www.mdpi.com/2227-9059/9/8/904pre-diabetesacute myocardial infarctionmetforminpericoronary fatsodium-glucose cotransporter 2 proteinleptin |
| spellingShingle | Celestino Sardu Nunzia D’Onofrio Michele Torella Michele Portoghese Simone Mureddu Francesco Loreni Franca Ferraraccio Iacopo Panarese Maria Consiglia Trotta Gianluca Gatta Marilena Galdiero Ferdinando Carlo Sasso Michele D’Amico Marisa De Feo Maria Luisa Balestrieri Giuseppe Paolisso Raffaele Marfella 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 Biomedicines pre-diabetes acute myocardial infarction metformin pericoronary fat sodium-glucose cotransporter 2 protein leptin |
| 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 | pre-diabetes acute myocardial infarction metformin pericoronary fat sodium-glucose cotransporter 2 protein leptin |
| url | https://www.mdpi.com/2227-9059/9/8/904 |
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