Impact Factor 3.394

The world's 3rd most-cited Physiology journal

Mini Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2018.01840

Mechanisms of Endothelial Dysfunction in Antiphospholipid Syndrome: Association with Clinical Manifestations

  • 1Departamento de Microbiología y Parasitología, Universidad de Antioquia, Colombia
  • 2Grupo de Inmunología Celular e Inmunogenética (GICIG), Universidad de Antioquia, Colombia
  • 3Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, Yale University, United States
  • 4Group of Research and Innovation in Vascular Health (GRIVAS-Heallth), Chile
  • 5Red Iberoamericana de alteraciones Vasculares Asociadas a TRastornos del EMbarazo (RIVA-TREM), Chile

The endothelium is a monolayer of cells that covers the inner surface of blood vessels and its integrity is essential for the maintenance of vascular health. Endothelial dysfunction is a key pathological component of antiphospholipid syndrome (APS). Its systemic complications include thrombotic endocarditis, valvular dysfunction, cerebrovascular occlusions, proliferative nephritis, deep vein thrombosis, and pulmonary embolism. In women, APS is also associated with pregnancy complications (obstetric APS). The conventional treatment regimens for APS are ineffective when the clinical symptoms are severe. Therefore, a better understanding of alterations in the endothelium caused by antiphospholipid antibodies (aPL) may lead to more effective therapies in patients with elevated aPL titers and severe clinical symptoms. Currently, while in vivo analyses of endothelial dysfunction in patients with APS have been reported, most research has been performed using in vitro models with endothelial cells exposed to either patient serum/plasma, monoclonal aPL, or IgGs isolated from patients with APS. These studies have described a reduction in endothelial cell nitric oxide synthesis, the induction of inflammatory and procoagulant phenotypes, an increase in endothelial proliferation, and impairments in vascular remodeling and angiogenesis. Despite these lines of evidence, further research is required to better understand the pathophysiology of endothelial dysfunction in patients with APS. In this review, we have compared the current understanding about the mechanisms of endothelial dysfunction induced by patient-derived aPL under the two main clinical manifestations of APS: thrombosis and gestational complications, either alone or in combination. We also discuss gaps in our current knowledge regarding aPL-induced endothelial dysfunction.

Keywords: Antiphospholipid Syndrome, Endothel dysfunction, antiphosholipid antibodies, Inflammation, Thrombosis

Received: 20 Jul 2018; Accepted: 06 Dec 2018.

Edited by:

Andrew P. Braun, University of Calgary, Canada

Reviewed by:

Owen L. Woodman, Baker Heart and Diabetes Institute, Australia
Jennifer A. Thompson, University of Calgary, Canada  

Copyright: © 2018 Velasquez Berrio, Rojas, Abrahams, Escudero and Cadavid J. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Angela P. Cadavid J, Departamento de Microbiología y Parasitología, Universidad de Antioquia, Medellin, Colombia, angela.cadavid@udea.edu.co