Potential Role and Impact of Peripheral Blood Mononuclear Cells in Radiographic Axial Spondyloarthritis-Associated Endothelial Dysfunction.

Patricia Ruiz-Limon,Alejandro Escudero-Contreras,Maria C Abalos-Aguilera,Clementina Lopez-Medina,Eduardo Collantes-Estevez,Chary Lopez-Pedrera,Yolanda Jimenez-Gomez,Isabel Arias-Quiros,Ivan Arias-De La Rosa,Maria L Ladehesa-Pineda,Carlos Perez-Sanchez,Rafaela Ortega-Castro,Nuria Barbarroja

doi:10.3390/diagnostics11061037

Abstract

Endothelial dysfunction (ED) is well known as a process that can lead to atherosclerosis and is frequently presented in radiographic axial spondyloarthritis (r-axSpA) patients. Here, we investigated cellular and molecular mechanisms underlying r-axSpA-related ED, and analyzed the potential effect of peripheral blood mononuclear cells (PBMCs) in promoting endothelial injury in r-axSpA. A total of 30 r-axSpA patients and 32 healthy donors (HDs) were evaluated. The endothelial function, inflammatory and atherogenic profile, and oxidative stress were quantified. In vitro studies were designed to evaluate the effect of PBMCs from r-axSpA patients on aberrant endothelial activation. Compared to HDs, our study found that, associated with ED and the plasma proatherogenic profile present in r-axSpA, PBMCs from these patients displayed a pro-oxidative, proinflammatory, and proatherogenic phenotype, with most molecular changes noticed in lymphocytes. Correlation studies revealed the relationship between this phenotype and the microvascular function. Additional in vitro studies confirmed that PBMCs from r-axSpA patients promoted endothelial injury. Altogether, this study suggests the relevance of r-axSpA itself as a strong and independent cardiovascular risk factor, contributing to a dysfunctional endothelium and atherogenic status by aberrant activation of PBMCs. Lymphocytes could be the main contributors in the development of ED and subsequent atherosclerosis in this pathology.

Highlights

Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton, frequently targeting the sacroiliac joints in the pelvis.Additional sites of involvement include the entheses and peripheral joints [1]
Patients displayed Endothelial dysfunction (ED), as shown by a substantial decrease in the rest flow (RF), the highest perfusion value after occlusion was released (Peak Flow, PF), the area of hyperemia (AH), the PF − RF, and the biological zero (BZ)-PF, as compared to healthy donors (HDs) (p < 0.05; a representative image is shown in Figure S1, Supplementary Materials)
To best of our knowledge, this is the first study to exhaustively explore the molecular profiles of peripheral blood mononuclear cells (PBMCs) associated with the proatherogenic status of radiographic axial spondyloarthritis (r-axSpA) patients, as well as their potential role in mediating endothelial injury in this disorder

Summary

Introduction

Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton, frequently targeting the sacroiliac joints in the pelvis.Additional sites of involvement include the entheses and peripheral joints [1]. R-axSpA patients have about twofold greater risk of premature mortality than the general population, which is mainly caused by an augmented cardiovascular (CV) risk [2,3,4]. There are several factors in r-axSpA that may lead to the development of atherosclerosis and cardiovascular disease (CVD). Traditional risk factors such as hypertension and an atherogenic lipid profile [5,6] play a crucial role, but do not fully explain the substantial burden of atherosclerosis detected in this disorder [7]. It is likely that the generalized inflammatory state renders these patients more prone to develop atherosclerotic CVD, as inflammatory mechanisms associated with atherosclerosis pathogenesis resemble those observed in rheumatology diseases [8,9]

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