scholarly journals 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 ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 904
Author(s):  
Celestino Sardu ◽  
Nunzia D’Onofrio ◽  
Michele Torella ◽  
Michele Portoghese ◽  
Simone Mureddu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Artery Bypass ◽  
Coronary Plaque ◽  
Diabetic Patients ◽  
Cardiac Events ◽  
Metformin Therapy ◽  
Protein Levels ◽  
Inflammatory Parameters ◽  
Sodium Glucose Cotransporter

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.

scholarly journals Pericoronary fat inflammation and Major Adverse Cardiac Events (MACE) in prediabetic patients with acute myocardial infarction: effects of metformin

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Celestino Sardu ◽  
Nunzia D’Onofrio ◽  
Michele Torella ◽  
Michele Portoghese ◽  
Francesco Loreni ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Adipose Tissue ◽  
Artery Bypass ◽  
Major Adverse Cardiac Events ◽  
Cardiac Events ◽  
Metformin Therapy ◽  
Adverse Cardiac Events ◽  
Factor Α

Abstract Background/objectives Pericoronary adipose tissue inflammation might lead to the development and destabilization of coronary plaques in prediabetic patients. Here, we evaluated inflammation and leptin to adiponectin ratio in pericoronary fat from patients subjected to coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). Furthermore, we compared the 12-month prognosis of prediabetic patients compared to normoglycemic patients (NG). Finally, the effect of metformin therapy on pericoronary fat inflammation and 12-months prognosis in AMI-prediabetic patients was also evaluated. Methods An observational prospective study was conducted on patients with first AMI referred for CABG. Participants were divided in prediabetic and NG-patients. Prediabetic patients were divided in two groups; never-metformin-users and current-metformin-users receiving metformin therapy for almost 6 months before CABG. During the by-pass procedure on epicardial coronary portion, the pericoronary fat was removed from the surrounding stenosis area. The primary endpoints were the assessments of Major-Adverse-Cardiac-Events (MACE) at 12-month follow-up. Moreover, inflammatory tone was evaluated by measuring pericoronary fat levels of tumor necrosis factor-α (TNF-α), sirtuin 6 (SIRT6), and leptin to adiponectin ratio. Finally, inflammatory tone was correlated to the MACE during the 12-months follow-up. Results The MACE was 9.1% in all prediabetic patients and 3% in NG-patients. In prediabetic patients, current-metformin-users presented a significantly lower rate of MACE compared to prediabetic patients never-metformin-users. In addition, prediabetic patients showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to NG-patients (P < 0.001). Prediabetic never-metformin-users showed higher inflammatory tone and leptin to adiponectin ratio in pericoronary fat compared to current-metformin-users (P < 0.001). Remarkably, inflammatory tone and leptin to adiponectin ratio was significantly related to the MACE during the 12-months follow-up. Conclusion Prediabetes increase inflammatory burden in pericoronary adipose tissue. Metformin by reducing inflammatory tone and leptin to adiponectin ratio in pericoronary fat may improve prognosis in prediabetic patients with AMI. Trial registration Clinical Trial NCT03360981, Retrospectively Registered 7 January 2018

Proteomic profiling of acute coronary thrombosis reveals a local decrease in pigment epithelium-derived factor in acute myocardial infarction

2012 ◽  
Vol 123 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Klaus Distelmaier ◽  
Christopher Adlbrecht ◽  
Johannes Jakowitsch ◽  
Oswald Wagner ◽  
Christopher Gerner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plaque Rupture ◽  
Coronary Thrombosis ◽  
Pigment Epithelium ◽  
Coronary Plaque ◽  
Diabetic Patients ◽  
Label Free ◽  
Proteomic Profiling ◽  
Pigment Epithelium Derived Factor

Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is considered the ultimate step in AMI (acute myocardial infarction). However, the precise pathophysiological mechanisms underlying acute coronary occlusion are not fully understood. We have analysed proteomic profiles of systemic plasma and plasma derived from the site of coronary plaque rupture of non-diabetic patients with STEMI (ST-segment elevation myocardial infarction). Label-free quantification of MS/MS (tandem MS) data revealed differential regulation of complement cascade components and a decrease in anti-thrombotic PEDF (pigment epithelium-derived factor) between CS (culprit site)-derived plasma and systemic plasma. PEDF, which is known to have a protective role in atherothrombosis, was relatively decreased at the CS, with a level of expression inverse to local MMP-9 (matrix metalloproteinase-9) activity. CS plasma displayed enhanced proteolytic activity towards PEDF. Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture.

Effect of the ACE Inhibitor Lisinopril on Mortality in Diabetic Patients With Acute Myocardial Infarction

Circulation ◽  
1997 ◽  
Vol 96 (12) ◽  
pp. 4239-4245 ◽  
Author(s):  
Giulio Zuanetti ◽  
Roberto Latini ◽  
Aldo P. Maggioni ◽  
MariaGrazia Franzosi ◽  
Luigi Santoro ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Ace Inhibitor ◽  
Diabetic Patients

scholarly journals Predictive value of stress hyperglycemia ratio for the occurrence of acute kidney injury in acute myocardial infarction patients with diabetes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Side Gao ◽  
Qingbo Liu ◽  
Hui Chen ◽  
Mengyue Yu ◽  
Hongwei Li
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Acute Kidney Injury ◽  
Cardiogenic Shock ◽  
Predictive Value ◽  
Kidney Injury ◽  
Left Ventricular Ejection ◽  
Diabetic Patients ◽  
Stress Hyperglycemia ◽  
Patients With Diabetes

Abstract Background Acute hyperglycemia has been recognized as a robust predictor for occurrence of acute kidney injury (AKI) in nondiabetic patients with acute myocardial infarction (AMI), however, its discriminatory ability for AKI is unclear in diabetic patients after an AMI. Here, we investigated whether stress hyperglycemia ratio (SHR), a novel index with the combined evaluation of acute and chronic glycemic levels, may have a better predictive value of AKI as compared with admission glycemia alone in diabetic patients following AMI. Methods SHR was calculated with admission blood glucose (ABG) divided by the glycated hemoglobin-derived estimated average glucose. A total of 1215 diabetic patients with AMI were enrolled and divided according to SHR tertiles. Baseline characteristics and outcomes were compared. The primary endpoint was AKI and secondary endpoints included all-cause death and cardiogenic shock during hospitalization. The logistic regression analysis was performed to identify potential risk factors. Accuracy was defined with area under the curve (AUC) by a receiver-operating characteristic (ROC) curve analysis. Results In AMI patients with diabetes, the incidence of AKI (4.4%, 7.8%, 13.0%; p < 0.001), all-cause death (2.7%, 3.6%, 6.4%; p = 0.027) and cardiogenic shock (4.9%, 7.6%, 11.6%; p = 0.002) all increased with the rising tertile levels of SHR. After multivariate adjustment, elevated SHR was significantly associated with an increased risk of AKI (odds ratio 3.18, 95% confidence interval: 1.99–5.09, p < 0.001) while ABG was no longer a risk factor of AKI. The SHR was also strongly related to the AKI risk in subgroups of patients. At ROC analysis, SHR accurately predicted AKI in overall (AUC 0.64) and a risk model consisted of SHR, left ventricular ejection fraction, N-terminal B-type natriuretic peptide, and estimated glomerular filtration rate (eGFR) yielded a superior predictive value (AUC 0.83) for AKI. Conclusion The novel index SHR is a better predictor of AKI and in-hospital mortality and morbidity than admission glycemia in AMI patients with diabetes.

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