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
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
Affiliations
Celestino Sardu
Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Nunzia D’Onofrio
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Michele Torella
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Michele Portoghese
Department of Cardiac Surgery, Santissima Annunziata Hospital, 07100 Sassari, Italy
Simone Mureddu
Department of Cardiac Surgery, Santissima Annunziata Hospital, 07100 Sassari, Italy
Francesco Loreni
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Franca Ferraraccio
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Iacopo Panarese
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Maria Consiglia Trotta
Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Gianluca Gatta
Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Marilena Galdiero
Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Ferdinando Carlo Sasso
Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Michele D’Amico
Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Marisa De Feo
Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Maria Luisa Balestrieri
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Giuseppe Paolisso
Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Raffaele Marfella
Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
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 p p 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.
