Plasma Levels of snoRNAs are Associated with Platelet Activation in Patients with Peripheral Artery Disease.

Anne Yaël Nossent,Thomas Gremmel,Neda Ektefaie,Johann Wojta,Simon Panzer,Christoph Kopp,Beate Eichelberger

doi:10.3390/ijms20235975

Abstract

In addition to supervised walking therapy, antithrombotic therapy and the management of risk factors, the treatment of peripheral artery disease (PAD) is limited to endovascular and surgical interventions, i.e., angioplasty with stent implantation and bypass surgery, respectively. Both are associated with a high restenosis rate. Furthermore, patients with PAD often suffer atherothrombotic events like myocardial infarction, transient ischemic attacks or stroke. Small ribonucleic acids (RNAs) have proven reliable biomarkers because of their remarkable stability. Small nucleolar RNAs (snoRNAs) guide modifications to small nuclear RNAs and ribosomal RNAs, enabling protein synthesis. In the current study, we measured four snoRNAs in 104 consecutive PAD patients who underwent elective infrainguinal angioplasty with stent implantation. We selected snoRNAs that showed significant overexpression in the plasma of end-stage PAD patients in a previous study. All four snoRNAs are transcribed from the 14q32 locus, which is strongly linked to human cardiovascular disease, including PAD and restenosis. We showed that the four selected 14q32 snoRNAs were abundantly expressed in the plasma of PAD patients. The plasma levels of these snoRNAs were not directly associated with target vessel restenosis, however, levels of SNORD113.2 and SNORD114.1 were strongly linked to platelet activation, which is an important determinant of long-term outcome, in PAD, and in cardiovascular disease in general.

Highlights

Peripheral artery disease (PAD) is caused by progressive atherosclerosis and is most frequently seen in the arteries of the lower extremities [1]
We recently showed that a set of small nucleolar ribonucleic acids (RNAs) had potential as biomarkers for muscle damage and repair in elite athletes and end stage peripheral artery disease (PAD) patients [9], as well as for the recovery of patients with ST-elevation myocardial infarction (STEMI) that underwent percutaneous coronary intervention (PCI) [10]
We aimed to evaluate the associations between Small nucleolar RNAs (snoRNAs) plasma levels with restenosis, MI and transient ischemic attacks (TIA)/stroke, and with classical risk factors for PAD development and progression, including smoking and platelet activation

Summary

Introduction

Peripheral artery disease (PAD) is caused by progressive atherosclerosis and is most frequently seen in the arteries of the lower extremities [1]. As the disease progresses and stenoses of the arteries increase, many patients experience pain at rest, referred to as critical limb ischemia. Patients with critical limb ischemia are at risk of developing non-healing wounds, ulcers and tissue necrosis often requiring amputation of the affected tissue [2]. In addition to supervised walking therapy, antithrombotic therapy and the management of cardiovascular risk factors, including smoking, hypertension, obesity and hypercholesterolemia, PAD treatment is limited to endovascular and surgical interventions, i.e., angioplasty with stent implantation and bypass surgery, respectively. Both are associated with a high restenosis/reocclusion rate [3]. Patients with PAD often suffer atherothrombotic events like myocardial infarction (MI), transient ischemic attacks (TIA) or stroke [2,4,5]

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