Background and Aims

Background: Systemic Lupus Erythematosus (SLE) patients are at risk for premature atherosclerosis at relatively young age. Endothelial dysregulation is one of the pathophysiologic mechanisms that lead to higher risk for cardiovascular disease in SLE.

Objectives: To perform a systematic literature review on endothelial markers that are dysregulated in SLE and investigate potential associations with disease activity.

Methods

Methods: Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of endothelial cell (EC) markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement.

Results

Results: From 1892 hits, 124 eligible articles were selected. The identified endothelial markers were involved in endothelial cell (EC) activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, GAS6, Thrombomodulin, VEGF, ICAM-1, and MCP-1. Other dysregulated markers, without associations with disease activity, were: Angiopoeitin-2, Neopterin, vWF, P-Selectin, VCAM-1, TWEAK, IP-10 and E-Selectin

Conclusions

Conclusions: We provide a complete literature overview for dysregulated endothelial markers in SLE comprising a wide range of different endothelial functions. SLE-induced endothelial marker dysregulation was seen with and without association with disease activity.Longitudinal data on endothelial markers in SLE are now needed to guide us in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients in young adulthood.