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

  • Velásquez M
  • Rojas M
  • Abrahams V
  • et al.
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Abstract

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.

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APA

Velásquez, M., Rojas, M., Abrahams, V. M., Escudero, C., & Cadavid, Á. P. (2018). Mechanisms of Endothelial Dysfunction in Antiphospholipid Syndrome: Association With Clinical Manifestations. Frontiers in Physiology, 9. https://doi.org/10.3389/fphys.2018.01840

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