MiR-126 Is an Independent Predictor of Long-Term All-Cause Mortality in Patients with Type 2 Diabetes Mellitus

Abstract

MicroRNAs are endogenous non-coding RNAs that are involved in numerous biological processes through regulation of gene expression. The aim of our study was to determine the ability of several miRNAs to predict mortality and response to antiplatelet treatment among T2DM patients. Two hundred fifty-two patients with diabetes were enrolled in the study. Among the patients included, 26 (10.3%) patients died within a median observation time of 5.9 years. The patients were receiving either acetylsalicylic acid (ASA) 75 mg (65%), ASA 150 mg (15%) or clopidogrel (19%). Plasma miR-126, miR-223, miR-125a-3p and Let-7e expressions were assessed by quantitative real time PCR and compared between the patients who survived and those who died. Adjusted Cox-regression analysis was used for prediction of mortality. Differential miRNA expression due to different antiplatelet treatment was analyzed. After including all miRNAs into one multivariate Cox regression model, only miR-126 was predictive of future occurrence of long-term all-cause death (HR = 5.82, 95% CI: 1.3–24.9; p = 0.024). Furthermore, miR-126, Let-7e and miR-223 expressions in the clopidogrel group were significantly higher than in the ASA group (p = 0.014; p = 0.013; p = 0.028, respectively). To conclude, miR-126 expression is a strong and independent predictor of long-term all-cause mortality among patients with T2DM. Moreover, miR-223, miR-126 and Let-7e present significant interactions with antiplatelet treatment regimens and clinical outcomes.

Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study

“…Recently it was described that miR-126 might be associated with CV events through modulation of platelet-mediated thrombin generation [ 14 , 34 ]. MiR-126 is highly expressed in endothelial cells and platelets and plays a pivotal role in vascular diseases and angiogenesis [ 16 , 17 , 21 , 35 ]. It is therefore possible that lower expression of P-selectin associated with higher expression levels of miR-126-5p in our study has been implicated in protective properties by suppressing NOTCH receptor 1 ( Notch1 ) homolog and reducing thrombogenicity in T2DM by targeting platelet tissue factor [ 43 ].…”

“…Mean values of all reactions—performed in triplicate—were used in statistical analysis as previously described [ 19 , 20 ]. MiRNA expressions were expressed as 2−ΔCT [ 19 , 21 , 22 ].…”

Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature

“…Furthermore, miR-126 is reported to be negatively correlated with vascular complications of T1DM, specifically retinopathy. MiR-144 expression patterns have been associated with diabetic heart disease, formation of reactive oxygen species and subsequently cell apoptosis, and miR-141 is found to play a significant role in the production of the inner mitochondrial membrane phosphate transporter in diabetic heart cells, directly affecting mitochondrial ATP production [64][65][66][67]. Although major progress has been accomplished, due to the knowledge gap surrounding miRNAs and their involvement in T1DM pathogenesis, further investigation of their implication in several T1DM stages, as well as in the regulation of key genes in disease onset and progression, is necessary.…”

Diagnostic and Prognostic Value of miRNAs after Coronary Artery Bypass Grafting: A Review

“…This finding arises from the fact that miR-126 mediated the production of chemokine CXCL2, which counteracts apoptosis and recruits progenitor cells in response to DNA damage or hypoxia [ 71 ]. We have also observed, among diabetes patients, that mir-126 expression was a strong independent predictor of long-term all-cause mortality [ 72 ].…”