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.

Highlights

  • Despite medical and technological developments, cardiovascular diseases are still the main causes of death worldwide [1]

  • Coronary and femoral artery stent implantations, any other heart or vascular surgical procedures, and toe or leg amputations were recorded as new cardiovascular events (CVEs)

  • We assessed the potential of miRNAs to predict post-surgery CVEs in Peripheral artery disease (PAD) patients by measuring miRNAs levels in the plasma and femoral atherosclerotic plaques and correlated the data with newly occurred CVEs during 1 year

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Summary

Introduction

Despite medical and technological developments, cardiovascular diseases are still the main causes of death worldwide [1]. Atherosclerosis is a multifactorial, chronic, inflammatory disorder that affects medium and large arteries in various vascular beds [2] It entails the accumulation of lipids in the arterial wall, a process that triggers a cascade of molecular and structural modifications that in the end leads to the obstruction of blood flow in the vessel, thrombus formation, and eventual rupture [3]. Peripheral artery disease (PAD) is an atherosclerotic disorder that affects arteries in the lower limbs and is one of the main causes of mortality and morbidity worldwide [4] It is caused by the partial or total obstruction of the arteries (usually the femoral artery), which in turn leads to severe ischemic conditions in the limbs [5]. Vital to understand the molecular mechanisms and the predictive factors underlying the development and progression of PAD in order to find new therapeutic approaches

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