Effects of metformin on changes of miR-19a and miR-221 expression associated with myocardial infarction in patients with type 2 diabetes.

BACKGROUND: The presence of hyperglycemia is a risk factor for cardiovascular diseases, as it increases the risk of myocardial infarction (MI). Metformin is considered an effective anti-hyperglycemic drug for patients with type 2 diabetes. Prediction of microRNAs is valuable in determining the risk of MI. AIM: This study aimed to measure the expression of two microRNAs, which are involved in the risk of MI and vascular stenosis among metformin users and non-users with MI. METHODS: In this study, we analyzed the expression of two microRNAs, collected from the blood samples of 180 subjects with MI, using the quantitative polymerase chain reaction (qPCR) assay. The subjects were categorized into three groups: non-diabetic patients with MI (MIND), diabetic patients with MI not using metformin (MIDMet-), and diabetic patients with MI using metformin (MIDMet+). To assess the sensitivity and specificity of miR-19a and miR-221 expression as potential biomarkers for MI, the receiver operating characteristic curve (ROC) analysis was conducted for both diabetic groups. RESULTS: The diabetic MIDMet + group exhibited a significant decrease in the expression levels of miR-221 (7.2 folds) and miR-19a (5.3 folds) as compared to the MIDMet- and MIND groups (p < 0.05). The ROC analysis revealed that the areas under the ROC curve (AUC) for circulating miR-19a and miR-221 were 0.931 and 0.965 in patients with type 2 diabetes, respectively (p < 0.001). CONCLUSION: Based on the present findings, metformin therapy can influence cardiovascular disorders and their outcomes through down-regulation of microRNAs. Also, exploration of microRNAs and the effects of metformin on their reduction can provide a potential therapeutic strategy for patients with type 2 diabetes by reducing the MI risk.

Decreased Expression of Cytotoxic T Lymphocyte-associated Protein 4: A Risk Factor of Myocardial Infarction.

Cardiovascular diseases are the most prevalent disease worldwide and pose a considerable threat to human health. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) plays a crucial role in the maintenance of immune diseases; however, its role in the progression of cardiovascular disorders is still unknown. The present study aimed to evaluate the relationship between CTLA-4 and myocardial infarction (MI). The Kyoto encyclopedia of genes and genomes database and the pathway studio database has revealed the role of CTLA4 as an inhibitory receptor on activated T cells. The relative expression of the CTLA-4 gene was assessed on the peripheral blood cells in 80 MI patients and 80 healthy individuals using quantitative real-time polymerase chain reaction (qRT-PCR) and also receiver operating characteristic (ROC) analysis was performed to evaluate the sensitivity and specificity of CTLA-4. We noticed the decreased expression of CTLA-4 levels in patients, compared to the control group (2.73±1.55 vs. 5.36±1.34). The study revealed the sensitivity of 0.89, specificity of 0.83, the accuracy of 0.9, and the area under the ROC curve (AUC) of 0.901 (95% CI: 0.727-0.776) for CTLA-4. The results highlighted the critical role of CTLA-4 as an inhibitory receptor in the maintenance of cardiovascular risks.

Up-Regulation of Cell-Free MicroRNA-1 and MicroRNA-221-3p Levels in Patients with Myocardial Infarction Undergoing Coronary Angiography.

Purpose: Myocardial infarction (MI), known as a multifactorial disease, remains the predominant cause of mortality and sudden deaths annually. The current study aimed to measure the expression of microRNA-1 and microRNA-221-3p in MI patients. Methods: In the current study, 100 healthy controls (with no history of heart disease) and 200 patients with MI were selected. Patients were divided into two groups based on angiography results: normal (no significant artery stenosis) and primary percutaneous coronary intervention (primary PCI, significant artery stenosis). The levels of microRNA-1 and microRNA-221-3p were quantified using real-time quantitative polymerase chain reaction. The correlation between levels of microRNAs and the common cardiac markers were analyzed statistically. Results: In comparison to fold change, microRNA-1 elevations were 8.5-fold in normal patients and 60-fold in patients with primary PCI; while microRNA-221-3p levels were 210- fold higher in primary PCI and 31.31-fold higher in normal cases compared with the healthy controls. Receiver operating characteristic analysis showed that the area under the curve (AUC) for circulating microRNA-1 and microRNA-221 were 0.903 and 0.958 in normal patients and 0.927 and 0.985 in primary PCI patients (p < 0.0001), respectively. Pearson correlation (ρ) analysis showed that circulation of microRNA-1 correlated with serum levels of cardiac troponin I (CTnI) (ρ =0.24), creatinine (ρ =0.34), creatinine kinase-myocardial band (CK-MB) (ρ =0.31), and microRNA-221-3p was significantly correlated with serum levels of CTnI (ρ =0.6), creatinine (ρ =0.41), and CK-MB (ρ =0.37), (P < 0.0001). Conclusion: The study underscored the potential of microRNA-1 and microRNA-221-3p as informative biomarkers and positively correlated with artery stenosis in MI.

Molecular miR-19a in Acute Myocardial Infarction: Novel Potential Indicators of Prognosis and Early Diagnosis.

OBJECTIVE: Due to the increasing annual incidence rate of disability and mortality in patients with acute myocardial infarction (AMI), the need for an appropriate diagnostic tool has become a crucial urgent issue. An increase in biomarkers and protein levels in response to AMI can be used as a predictive biomarker with different sensitivities and specificities. This study aimed at investigating the role of miR-19a as a biomarker with acceptable sensitivity and specificity for early diagnosis of AMI. METHODS: We studied 175 patients with AMI admitted within 12 h of symptom onset and 90 healthy subjects as control group. Patients were divided into two groups, including group I (normal vessels and no significant artery stenosis) and primary percutaneous coronary intervention (PCI) group II (patients with more than 50% stenosis in vessels and severe atherosclerosis) diagnosed by angiography. The expression level of miR-19a was evaluated by the real-time polymerase chain reaction and other serum chemistries were also analyzed. RESULTS: The results demonstrated that circulating miR-19a levels were significantly increased in patient groups compared to the control group (2.88 ± 1.06 vs. 5.93 ± 1.28, P<0.0001). We also found that miR-19a levels were higher in group II (134.62-fold) than group I (15.42-fold). The upper levels of miR-19a were significantly correlated with the increased serum levels of CK-MB (ρ=0.29, P<0.0001), CTn I (ρ=0.4, P<0.0001) and creatinine (ρ=0.27, P<0.0001). In addition, Receiver Operating Characteristic (ROC) analysis revealed that circulating miR-19a had considerable diagnostic accuracy for the patients with normal vessel with an AUC of 0.930 (95% CI: 0.697-0.765) and for PCI patients with an AUC of 0.966 (95% CI: 0.748-0.784). CONCLUSION: Circulating miR-19a possibly has prognostic value to be used as a promising molecular target for early diagnosis and prognosis of AMI.