Dysregulated endothelial cell markers in systemic lupus erythematosus: a systematic review and meta-analysis

To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Search...

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Bibliographic Details
Published in:	Journal of inflammation (London, England) Vol. 20; no. 1; p. 18
Main Authors:	Bergkamp, S C, Wahadat, M J, Salah, A, Kuijpers, T W, Smith, V, Tas, S W, van den Berg, J M, Kamphuis, S, Schonenberg-Meinema, D
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 16-05-2023 BioMed Central BMC
Subjects:	Age Analysis Angiogenesis Antibodies Apoptosis Arteriosclerosis Atherosclerosis Biomarkers Cardiac patients Cardiovascular disease Cell adhesion & migration Cytokines Development and progression Diagnosis E-selectin Endothelial cell Endothelial cell markers Endothelial cells Endothelium Inflammation Inflammatory diseases Intercellular adhesion molecule 1 IP-10 protein Literature reviews Lupus Medical research Medicine, Experimental Meta-analysis Monocyte chemoattractant protein 1 P-selectin Pentraxins Premature atherosclerosis Review Systematic review Systemic lupus erythematosus Vascular cell adhesion molecule 1 Vascular endothelial growth factor Premature atherosclerosis Cardiovascular disease Endothelial cell Endothelial cell markers Systemic lupus erythematosus
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Summary:	To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. 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 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. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman's rank or Pearson's) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in 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, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	1476-9255 1476-9255
DOI:	10.1186/s12950-023-00342-1