Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus

Abstract

Patients with systemic lupus erythematosus (SLE) have accelerated cardiovascular disease and dysfunctional endothelial repair mechanisms. Myeloid angiogenic cells (MACs), derived from circulating monocytes, augment vascular repair by paracrine secretion of pro-angiogenic factors. We observed that SLE MACs are dysfunctional and secrete pro-inflammatory cytokines. We also found that the vitamin D receptor was transiently expressed during MAC differentiation and that in vitro, calcitriol increased differentiation of monocytes into MACs in both SLE and in a model using the prototypic SLE cytokine, interferon-alpha. The active form of vitamin D (calcitriol) restored the SLE MAC phenotype towards that of healthy subjects with reduced IL-6 secretion, and normalised surface marker expression. Calcitriol also augmented the angiogenic capacity of MACs via the down-regulation of CXCL-10. In SLE patients treated with cholecalciferol for 12 weeks, the improvement in endothelial function correlated with increase in serum 25(OH)D concentrations independently of disease activity. We also show that MACs were able to positively modulate eNOS expression in human endothelial cells in vitro, an effect further enhanced by calcitriol treatment of SLE MACs. The results demonstrate that vitamin D can positively modify endothelial repair mechanisms and thus endothelial function in a population with significant cardiovascular risk.

Brief Report: Vitamin D Deficiency Is Associated With Endothelial Dysfunction and Increases Type I Interferon Gene Expression in a Murine Model of Systemic Lupus Erythematosus

“…In that study, patients with an increase in flow‐mediated dilation (FMD) had significantly higher posttreatment 25(OH)D levels, although there was no clear correlation between 25(OH)D levels and changes in FMD. In a larger observational study of 40 patients, a significant association between changes in serum 25(OH)D levels and FMD improvement was demonstrated over 12 weeks, accompanied by increased numbers of proangiogenic myeloid cells, implicating that changes in endothelial repair were involved . Results from these 2 small clinical studies suggest that vitamin D therapy can modify endothelial function and, thus, potentially reduce CVD risk in patients with SLE.…”

Vitamin D deficiency is independently associated with greater prevalence of erectile dysfunction: The National Health and Nutrition Examination Survey (NHANES) 2001–2004

“…34 One mechanism linking low vitamin D levels with ED may be via reduced synthesis of nitric oxide. Secretion of nitric oxide is needed for relaxation of the smooth muscles of the corpora cavernosa and subsequent penile erection, and vitamin D may be a regulator of endothelial nitric oxide synthase.…”

Vitamin D Ameliorates Angiotensin II-Induced Human Endothelial Progenitor Cell Injury via the PPAR-γ/HO-1 Pathway

“…Furthermore, vitamin D deficiency has been identified as a risk factor for myocardial infarction, heart failure, and inflammatory cardiovascular disease [12-14]. Clinical reports have confirmed that vitamin D could regulate blood pressure in healthy individuals [15] and decrease high blood pressure in patients [15, 16].…”