Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events

Abstract

There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients.

miR-146a-5p, miR-223-3p and miR-142-3p as Potential Predictors of Major Adverse Cardiac Events in Young Patients with Acute ST Elevation Myocardial Infarction—Added Value over Left Ventricular Myocardial Work Indices

“…miR-142-3p, known to be involved in atherosclerosis [ 55 ] and ischemic heart disease [ 35 ] proved to be an independent prognostic marker of adverse outcome in our group of young patients with STEMI. Its prognostic value was tested using an ROC curve analysis, where we obtained an AUC of 0.732 (95% CI), p = 0.031, and determined an optimal cut-off value of 1115 (sensitivity 77.8%, specificity 68.3%) for MACE prediction.…”

“…The data were analysed using ViiA7 Software v1.2 with the automatic Cq setting. The expression level of each miRNA was determined relative to that of exogenously added cel-miR-39-2p (ID 000200) as previously reported [ 55 ].…”

Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis

“…Moreover, upregulated miR-92a is considered as a differential biomarker for UA [144]. However, miR-92a expression decreased in the blood of patients with CAD [108,111,154], CHD [112] and atherosclerosis [155], in plasma and atherosclerotic plaques in PAD patients with cardiovascular events (CVEs) [156].…”

“…In THP-1 macrophages, miR-212 targeted SIRT1, which led to inhibition of ABCA1 expression, decreased cholesterol efflux and increased intracellular lipid accumulation [190]. [191], in serum, in the vascular wall of patients with atherosclerosis obliterans [192], in the plasma of patients with AMI [115], PAD with cardiovascular events (CVEs) [156], unstable coronary artery disease (UCAD) [193], coronary artery calcification (CAC) [194] and UA [99,105], in platelets of patients with CAD [195], in atherosclerotic plaques of patients with PAD with cardiovascular events (CVEs) [156], and in aneurysm tissues of patients with AAA [119]. HDL-transported miR-223 elevated in patients with hypercholesterolemia and in Ldlr −/− and ApoE −/− mice on a high-fat diet.…”

miRNA Regulatory Networks Associated with Peripheral Vascular Diseases

“…Many studies have indicated an important role of miRNAs in vascular pathology [ 25 , 26 , 27 , 28 ] and have pointed to certain dysregulated miRNAs as candidates for biomarkers of LEAD [ 29 , 30 ], AAA [ 31 ], and CVD [ 32 , 33 , 34 ]. Special attention is paid to the identification of circulatory miRNA biomarkers (from whole blood, blood cells, plasma, or serum) with potential utility as diagnostic, prognostic, and therapeutic targets for these diseases [ 35 , 36 , 37 , 38 , 39 , 40 ].…”