Pentraxin 3 (PTX3): A Molecular Marker of Endothelial Dysfunction in Chronic Migraine.

Clara Domínguez-Vivero,Xiana Rodríguez-Osorio,Tomás Sobrino,Marta Saavedra,José Castillo,Francisco Campos,Yago Leira,Rogelio Leira,Ana López-Ferreiro

doi:10.3390/jcm9030849

Abstract

Even though endothelial dysfunction is known to play a role in migraine pathophysiology, studies regarding levels of endothelial biomarkers in migraine have controversial results. Our aim was to evaluate the role of pentraxin 3 (PTX3) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) as potential biomarkers of endothelial dysfunction in chronic migraine (CM). We performed a case-control study including 102 CM patients and 28 control subjects and measured serum levels of markers of endothelial dysfunction (PTX3 and sTWEAK) and inflammation [high-sensitivity C-reactive protein (hs-CRP)] as well as brachial artery flow-mediated dilation (FMD) during interictal periods. Interictal serum levels of PTX3 and sTWEAK were higher in CM patients than in controls (1350.6 ± 54.8 versus 476.1 ± 49.4 pg/mL, p < 0.001 and 255.7 ± 21.1 versus 26.4 ± 2.6 pg/mL, p < 0.0001; respectively). FMD was diminished in CM patients compared to controls (9.6 ± 0.6 versus 15.2 ± 0.9%, p < 0.001). Both PTX3 and sTWEAK were negatively correlated with FMD (r = −0.508, p < 0.001 and r = −0.188, p = 0.033; respectively). After adjustment of confounders, PTX3 remained significantly correlated to FMD (r = −0.250, p = 0.013). Diagnosis of CM was 68.4 times more likely in an individual with levels of PTX3 ≥ 832.5 pg/mL, suggesting that PTX3 could be a novel biomarker of endothelial dysfunction in CM.

Highlights

Migraine is a neurological disorder that involves vascular and neural mechanisms in its pathophysiology
We demonstrated that pentraxin 3 (PTX3) and sTWEAK are elevated in chronic migraine (CM) patients and that high plasma levels of PTX3 can predict a good response to OnabotulinumtoxinA (OnabotA), which is widely used for the treatment of CM [18]
The present study follows this line of research and shows that plasma PTX3 is significantly correlated with endothelial function assessed by flow-mediated dilation (FMD) in patients with CM, pointing to this as the most probable underlying mechanism

Summary

Introduction

Migraine is a neurological disorder that involves vascular and neural mechanisms in its pathophysiology. Promising biomarkers demand further investigation in the migraine population, for instance, brachial artery flow-mediated dilation (FMD) This technique has emerged as the most widely used non-invasive tool to assess endothelial function [5]. Two studies have demonstrated higher plasma levels of PTX3 in migraine patients during attacks when compared to interictal periods [11] or healthy controls [12]. Plasma levels of soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) have been analysed as potential biomarkers of cardiovascular disease and endothelial dysfunction in vascular [13,14,15] and non-vascular diseases [16]. The aim of this study, was to investigate the relationship between levels of PTX3 and sTWEAK and FMD in order to elucidate their potential role as markers of endothelial dysfunction in CM patients during interictal periods

Experimental Section

Findings

Conclusions