Background: Systemic lupus erythematosus (SLE) is associated with a high prevalence of cardiovascular disease. Circulating endothelial progenitor cells (EPCs) contribute to vascular regeneration and repair, thereby protecting against atherosclerotic disease. EPCs are derived from CD34+ haematopoietic stem cells (HSCs), which have an increased propensity for apoptosis in the bone marrow of patients with SLE.
Aim: To determine whether circulating HSCs and EPCs are reduced in SLE, contributing to an increased cardiovascular risk.
Methods: Progenitor cells were sampled from 15 female patients with SLE in prolonged clinical remission from their disease and 15 matched healthy controls. HSC and CD34+KDR+ EPCs were quantified by flow cytometry. Annexin V staining was used to identify apoptotic cells.
Results: Patients with SLE had reduced levels of circulating CD34+ HSCs and CD34+KDR+ EPCs, associated with increased HSC apoptosis. Compared with controls, the fraction of HSCs that could be identified as EPCs was higher in patients with SLE, consistent with a primary defect of HSCs. EPC outgrowth from mononuclear cells, which depends mainly on CD34− cells, was unaffected.
Conclusions: Patients with SLE have lower levels of circulating HSCs and EPCs, even during clinical remission. The data suggest that increased HSC apoptosis is the underlying cause for this depletion. These observations indicate that progenitor cell-mediated endogenous vascular repair is impaired in SLE, which may contribute to the accelerated development of atherosclerosis.
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- 7-AAD, 7-amino-actinomycin-D
- ABI, Ankle-Brachial Index
- AI, Augmentation Index
- CVD, cardiovascular disease
- EPCs, endothelial progenitor cells
- FITC, fluorescein isothiocyanate
- FS, forward scatter
- HSCs, haematopoietic stem cells
- HUVECs, human umbilical vein endothelial cells
- KDR, kinase domain receptor
- PE, phycoerythrin
- PWV, pulse wave velocity
- SS, sideward scatter
- SLE, systemic lupus erythematosus
- SLEDAI, Systemic Lupus Erythematosus Disease Activity Index
- VEGF, vascular endothelial growth factor
Published Online First 28 February 2007
Competing interests: None declared.
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