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Endothelial function and endothelial progenitor cells in systemic lupus erythematosus

Abstract

The observations that traditional cardiovascular disease (CVD) risk factors fail to fully account for the excessive cardiovascular mortality in patients with systemic lupus erythematosus (SLE) compared with the general population have prompted in-depth investigations of non-traditional, SLE-related risk factors that contribute to cardiovascular complications in patients with SLE. Of the various perturbations of vascular physiology, endothelial dysfunction, which is believed to occur in the earliest step of atherosclerosis, has been extensively investigated for its contribution to CVD risk in SLE. Endothelial progenitor cells (EPCs), which play a crucial part in vascular repair, neovascularization and maintenance of endothelial function, are quantitatively and functionally reduced in patients with SLE. Yet, the lack of a unified definition of EPCs, standardization of the quantity and functional assessment of EPCs as well as endothelial function measurement pose challenges to the translation of endothelial function measurements and EPC levels into prognostic markers for CVD in patients with SLE. This Review discusses factors that contribute to CVD in SLE, with particular focus on how endothelial function and EPCs are evaluated currently, and how EPCs are quantitatively and functionally altered in patients with SLE. Potential strategies for the use of endothelial function measurements and EPC quantification as prognostic markers of CVD in patients with SLE, and the limitations of their prognostication potential, are also discussed.

Key points

  • Traditional cardiovascular disease (CVD) risk factors are prevalent in patients with systemic lupus erythematosus (SLE), but this observation cannot fully explain the excess of cardiovascular mortality and morbidity in these patients.

  • Endothelium-dependent flow-mediated dilation of the brachial artery, a common biophysical measure of endothelial function, is impaired in patients with SLE, even if they do not present with CVD.

  • Impaired endothelial function is associated with increased diastolic blood pressure, inflammation and vertebral bone loss in patients with SLE.

  • Endothelial progenitor cells (EPCs) are reduced quantitatively and functionally in patients with SLE, compared with healthy individuals.

  • Antimalarial drug use might be associated with elevation of levels of circulating angiogenic cells in patients with SLE.

  • Standardization of the definition and functional characterization of EPCs is paramount before EPCs can be used as prognostic biomarkers for CVD in patients with SLE.

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Fig. 1: Relationships between endothelial function, EPCs and CVD in SLE.
Fig. 2: Type 1 interferon and other key mediators detrimental to endothelial cells and EPCs.
Fig. 3: Factors that influence endothelial function in SLE.
Fig. 4: Regulation of EPCs by different therapeutic approaches and their prognostic potential for CVD in SLE.

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Acknowledgements

The authors would like to thank A-M. Fairhurst, for her expert contributions of flow cytometry evaluation of CD34+–CD133+–CD309+ circulating angiogenic cells, and L-H. Ling, and his team for their contributions of flow-mediated dilation measurement of our patients with SLE, and for his expert input into the information presented in Table 1.

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A.M. conceptualized the framework and content of the article; A.M. and J.K.Y.C. researched data for the article, made substantial contributions to discussions of the content, co-wrote the article, reviewed and edited the manuscript before submission.

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Correspondence to Anselm Mak.

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A.M. received consulting fees from Janssen and GlaxoSmithKline, and a research fund from GlaxoSmithKline for investigator-sponsored research through the GSK Supported Studies Programme (Proposal ID 10743). J.K.Y.C. received salary support from Singapore’s Ministry of Health’s National Medical Research Council (NMRC-CSA-SI-008/2016).

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Mak, A., Chan, J.K.Y. Endothelial function and endothelial progenitor cells in systemic lupus erythematosus. Nat Rev Rheumatol 18, 286–300 (2022). https://doi.org/10.1038/s41584-022-00770-y

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