Session Type: Abstract Submissions (ACR)
Patients with Systemic Lupus Erythematosus (SLE) have an increased prevalence of cardiovascular disease (CVD). Vitamin D deficiency is common in SLE and an independent risk factor for CVD in the general population. We have previously shown that low vitamin D is associated with arterial stiffness in SLE patients.
Myeloid angiogenic cells (MACs) have an important role in endothelial repair in animal models. Preliminary studies have demonstrated impaired function of these cells in lupus. Myeloid cells are able to respond to vitamin D in vitro and express functional vitamin D receptors. We propose that vitamin D may have beneficial effects on MAC function and thus endothelial repair.
Peripheral blood mononuclear cells (PBMCs) from vitamin D deficient (<20ng/ml) SLE patients, or vitamin D-replete (>20ng/ml) healthy controls, were cultured for 7 days on fibronectin in endothelial growth media +/- 1,25(OH)2D3 (0.1-100nM). For survival studies, the number of cells able to uptake LDL was enumerated in random fields. Surface CD marker expression (CD14, CD68, CD86, CCR7, CD206) in MACs was determined using real-time quantitative PCR. Angiogenic factor secretion was measured using a Bio-Plex®Human Angiogenesis Suspension Array. Angiogenic function of MACs was determined using human aortic endothelial cells in a Matrigel model. Data were analysed using linear regression, paired t tests and one-way ANOVA where appropriate.
MACs expressed high levels of CD206, and low CCR7 compared to PBMCs consistent with an M2 macrophage phenotype. Phagocytosis was demonstrated by MAC uptake of FITC-labelled beads. MAC secreted IL-8 (mean [sd] 13.9 [20.1] ug/ml) , VEGF (37.2 [26.1] pg/ml), HGF (1414  pg/ml), leptin (209  pg/ml), and PDGF (564  pg/ml) but not GCSF or angiopoetin.
Vitamin D (0.1-100nM) increased the number of lupus MAC on day 8 in those with a low number (<150/field) at baseline (p=0.037) in a dose-dependent manner. This effect was replicated in healthy MACs treated with 0.1ng/ml interferon-α2b (p=<0.001). Expression of all macrophage markers was reduced by vitamin D (10nM) but the M2 marker CD206 was preferentially reduced compared to M1 markers CCR7 (p=0.008) and CD86 (p=0.043).
Conditioned media from vitamin D (10nM) treated SLE MACs further increased endothelial tubule network density in the angiogenesis model (mean [sd] relative density 1.43 [0.12] vs 1.66 [0.15], p=0.012) compared to untreated SLE MACS. Vitamin D alone, however, did not increase tubule density (0.96 [0.10], p=0.582). In the Bio-Plex array, secretion of any of the angiogenic factors by MACs was not directly affected by vitamin D.
MACs are population of M2 macrophages with angiogenic capacity in vitro. Vitamin D increases the number of lupus MACs and changes the surface maker profile. The angiogenic capacity of MACs was increased by vitamin D ex vivo, but this was not due to changes in expression of common angiogenic factors. Further work will identify the mechanism by which vitamin D may augment endothelial repair in patients with SLE.
J. A. Reynolds,
D. W. Ray,
M. Y. Alexander,
I. N. Bruce,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/vitamin-d-increases-the-number-and-function-of-myeloid-angiogenic-cells-in-systemic-lupus-erythematosus/