TY - JOUR
T1 - Dysregulated endothelial cell markers in systemic lupus erythematosus
T2 - a systematic review and meta-analysis
AU - Bergkamp, S. C.
AU - Wahadat, M. J.
AU - Salah, A.
AU - Kuijpers, T. W.
AU - Smith, V.
AU - Tas, S. W.
AU - van den Berg, J. M.
AU - Kamphuis, S.
AU - Schonenberg-Meinema, D.
N1 - Funding Information: The authors of this manuscript would like to express our gratitude to the librarian(s) of the Erasmus Medical Centre, Mrs. S. Meertens-Gunput, PhD and Amsterdam UMC, Mr. R. Spijker, PhD. We would also like to thank M.D.J. Wolvers, PhD, and J.A. ter Schure, PhD, for their advices on statistics for the meta-analyses. We would like to thank Mr. R. Suurmond, Assistant Professor, PhD, Maastricht University, creator of the Meta-Essentials Tool, and M.W.T. Tanck, Assistant Professor, PhD, Department of Clinical Epidemiology, Biostatistics and Bioinformatics at Amsterdam University Medical Centres, for their methodological and statistical advice on the meta-analyses. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Objectives: 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. 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 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. Results: 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. Conclusions: 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.
AB - Objectives: 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. 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 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. Results: 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. Conclusions: 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.
KW - Cardiovascular disease
KW - Endothelial cell
KW - Endothelial cell markers
KW - Premature atherosclerosis
KW - Systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=85159595487&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s12950-023-00342-1
DO - https://doi.org/10.1186/s12950-023-00342-1
M3 - Review article
C2 - 37194071
SN - 1476-9255
VL - 20
JO - Journal of inflammation (London, England)
JF - Journal of inflammation (London, England)
IS - 1
M1 - 18
ER -