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

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

Association of the A561C E-selectin polymorphism with systemic lupus erythematosus in 2 independent populations

Objective. E-selectin is expressed on cytokine stimulated endothelial cells and plays an important role in leukocyte-endothelium interactions and inflammatory cell recruitment. The gene for E-selectin is located at chromosome 1q23-25 within the linkage area for systemic lupus erythematosus (SLE). The best characterized polymorphism in E-selectin molecule is A561C. which codes for Ser128Arg. We studied the prevalence of the A561C E-selectin gene polymorphism in patients with SLE and controls from 3 different ethnic populations

The association between metabolic syndrome and its components with systemic lupus erythematosus: a comprehensive systematic review and meta-analysis of observational studies

Objectives: Based upon inflammatory-related factors in chronic systemic lupus erythematosus (SLE), as well as the long-term prescription of corticosteroids, metabolic syndrome (MetS) prevalence is expected to be higher in SLE patients than among those without SLE. The aim of this study was to systematically analyze: (1) the worldwide prevalence of MetS in patients with SLE using different criteria, (2) the risk of MetS in patients with SLE compared with those without SLE, and (3) the risk of MetS component in patients with SLE compared with healthy controls. Methods: We searched international databases, such as: Web of Science, Medline, PubMed, Scopus, Embase, CABI, CINAHL, DOAJ and Google Scholar. The articles which reported the prevalence of MetS in SLE patients, between 2006 and 2017, were included in the study if they had a: clear study design, study time and location, sound sampling approach and appropriate statistical analyses. Studies without sufficient data to determine the prevalence of MetS were excluded. Also, studies in patients suffering from other clinical diseases were not included. Results: The meta-analyses of the prevalence (40 studies (n = 6085)) and risk (20 studies (n = 2348)) of MetS in SLE patients were conducted separately. The pooled prevalence of MetS among SLE patients was found to be 26% (95% confidence interval (CI): 22-30%), but varied from 18% (95% CI: 11-25%) to 34% (95% CI: 25-42%), depending upon the diagnostic criteria used. The overall pooled odds ratio (OR) of MetS in SLE patients, compared with healthy controls, was (OR = 2.50; 95% CI: 1.86-3.35), but this ranged from (OR = 1.23; 95% CI: 0.61-2.49) to (OR = 10.71; 95% CI: 1.33-86.48), depending upon the criteria used. Also, the risk of high fasting blood sugar (FBS; OR = 1.59; 95% CI: 1.05-2.40), low high-density lipoprotein cholesterol (HDL-C; OR = 1.43; 95% CI: 1.02-2.01), high blood pressure (BP; OR = 2.76; 95% CI: 2.19-3.47), high triglycerides (TG; OR = 2.85; 95% CI: 2.05-3.95) and high waist circumference (WC; OR = 1.37; 95% CI: 0.97-1.94) were all found to be higher in SLE patients compared with healthy controls. Conclusions: The risk of MetS was significantly higher in SLE patients, compared with healthy controls, even after adjusting for publication bias. Among MetS components, high TG and high BP were most strongly associated with SLE. Considering that high TG and high BP are preventable, there is an international need to implement effective interventions to reduce MetS components in SLE patients in order to prevent serious outcomes such as cardiovascular diseases and mortality