1,25‐Dihydroxyvitamin D<sub>3</sub> inhibits tumor necrosis factor‐α‐induced adhesion molecule expression in endothelial cells

Martinesi, Maria; Bruni, Sara; Stio, Maria; Treves, Cristina

doi:10.1016/j.cellbi.2006.01.004

Cited by 81 publications

(66 citation statements)

References 44 publications

(47 reference statements)

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“…Our results are surprising given the available biologic evidence supporting a role for vitamin D in modulating vascular function. This evidentiary trail includes in vitro findings of vitamin D receptors on human endothelial cells, the ability of active vitamin D to inhibit the expression of adhesion molecules on these cells, 24,25 and in vivo studies in animals demonstrating reductions of blood pressure and endothelial-dependent contractions in spontaneously hypertensive rats treated chronically with vitamin D. 26,27 Additionally, recent observational and small interventional trials have linked low vitamin D status to poor vascular health, 28 and vitamin D sufficiency or repletion to improvement in brachial artery flow-mediated vasodilatation (FMD), reactive hyperemia index, aortic stiffness, and blood pressure. [28][29][30] These studies, however, were crosssectional/observational, 28 non-randomized, and included only healthy asymptomatic subjects 29 and adolescents.…”

Section: Discussionmentioning

confidence: 99%

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease

et al. 2012

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Adequate vitamin D levels may promote cardiovascular health by improving endothelial function and down-regulating inflammation. The objective of this pilot trial was to investigate the effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease (CAD). Using a double-blind placebo wait-list control design, 90 subjects with CAD and vitamin D deficiency (< 20 ng/ml) were randomized 1:1 to 50,000 IU of oral ergocalciferol or placebo weekly for 12 weeks. Endothelial function (reactive hyperemia peripheral arterial tonometry, RH-PAT), circulating adhesion molecules, and pro-inflammatory cytokines were measured at baseline and 12 weeks. The median increase in serum 25-vitamin D from baseline was 26 ± 17 ng/ml in the active group and 4 ± 8 ng/ml in the placebo group (between-group difference = 22 ng/ml, p < 0.001). The median within-subject change in RH-PAT score was 0.13 ± 0.73 with active treatment and −0.04 ± 0.63 with placebo (between-group difference = 0.17, p = 0.44). Within-group and between-group differences in intercellular adhesion molecule levels were greater with placebo (between-group difference = 6 ng/ml, p = 0.048). Vascular cell adhesion molecule levels decreased in both groups by a similar magnitude (median difference between groups = 8.5 ng/ml, p = 0.79). There was no difference between groups in magnitude of reduction in interleukin (IL)-12 (−8.6 ng/ml, p = 0.72) and interferon-gamma (0.52 ng/ml, p = 0.88). No significant differences in blood pressure, e-selectin, high-sensitivity c-reactive protein, IL-6 or the chemokine CXCL-10 were found with treatment. In conclusion, repleting vitamin D levels in subjects with CAD failed to demonstrate any benefits on surrogate markers of cardiovascular health. These results question the role of vitamin D supplementation in modifying cardiovascular disease. ClinicalTrials.gov Identifier: NCT01570309.

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Section: Discussionmentioning

confidence: 99%

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease

et al. 2012

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“…In patients with end-stage renal disease, calcidiol and calcitriol levels are inversely correlated with atherosclerosis and endothelial dysfunction (66). Furthermore, VDRAs downregulate LPS-induced immune activation of endothelial cells (28) and inhibit TNF-␣-induced adhesion molecules expression in cultured endothelial cells (71). Mice lacking VDRs show lower platelet aggregation and higher fibrin formation in the liver and kidney after LPS administration (2), suggesting an important role for VDRA on endothelial dysfunction.…”

Section: Role Of Vdra In the Vasculaturementioning

confidence: 99%

A new role for vitamin D receptor activation in chronic kidney disease

Valdivielso

Cannata-Andía

Coll

et al. 2009

American Journal of Physiology-Renal Physiology

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Valdivielso JM, Cannata-Andía J, Coll B, Fernández E. A new role for vitamin D receptor activation in chronic kidney disease. Am J Physiol Renal Physiol 297: F1502-F1509, 2009. First published July 22, 2009 doi:10.1152/ajprenal.00130.2009.-Vitamin D has proven to be much more than a simple "calcium hormone." The fact that the vitamin D receptor has been found in cells not related to mineral metabolism supports that statement. The interest of nephrologists in vitamin D and its effects beyond mineral metabolism has increased over the last few years, evidencing the importance of this so-called "sunshine hormone." In the present review, we highlight the most recent developments in the traditional use of vitamin D in chronic kidney disease (CKD) patients, namely, the control of secondary hyperparathyroidism (sHPT). Furthermore, we also explore the data available regarding the new possible therapeutic uses of vitamin D for the treatment of other complications present in CKD patients, such as vascular calcification, left ventricular hypertrophy, or proteinuria. Finally, some still scarce but very promising data regarding a possible role of vitamin D in kidney transplant patients also are reviewed. The available data point to a potential beneficial effect of vitamin D in CKD patients beyond the control of mineral metabolism.VITAMIN D IS A STEROID HORMONE that has long been known for its important role in regulating body levels of calcium (Ca) and phosphorus (P) and in mineralization of bone. However, there is an increasing amount of data proving that vitamin D exerts its effects beyond kidney, intestine, and bone (Fig. 1). The active form of vitamin D (calcitriol) mediates its biological effects by binding to the vitamin D receptor (VDR), which then translocates to the nuclei of target cells (for review, see Ref. 47). The VDR is a ligand-activated transcription factor that, after activation, recruits cofactor molecules and binds to specific DNA binding sites to modify the expression of target genes. Ligand-mediated conformational changes of the VDR contribute to specific mechanisms in its signaling cascade. Thus the structural chemical modification of active vitamin D is a powerful tool in discovering new compounds that show selective activation of the VDR. Over the last years, a number of new VDR activators (VDRAs), defined as compounds that can bind to VDR and induce its activation, have been synthesized and used in several diseases, including in patients with CKD. Their potential as new therapeutic agents has boosted this area of research. Moreover, new evidence suggests that VDR polymorphisms may influence the response to VDRAs (125). Present Use of VDRAs in Patients with CKDOne of the main complications in patients with CKD is the development of secondary hyperparathyroidism (sHPT). In the past, the increase in parathyroid gland (PTG) size and parathyroid hormone (PTH) synthesis were attributed to a decrease in circulating Ca. As a result, patients with sHPT were treated with oral vitamin D metabolites to correct ...

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“…31 In human umbilical vein endothelial cells, the increase of VCAM-1 and ICAM-1 induced by TNF-a were inhibited by 1a,25-(OH) 2 D 3 . 32 The present study first showed that the active form of vitamin D directly influences BBB endothelial cells through the upregulation of tight junction proteins and downregulation of cell adhesion molecules under TNF-a stimulation. We incubated 1a,25-(OH) 2 [36][37][38][39] In the present study, we observed that 1a,25-(OH) 2 D 3 restored the decrease of claudin-5 and ZO-1 in the cells induced by RRMS sera.…”

Section: Discussionmentioning

confidence: 99%

Active form of vitamin D directly protects the blood–brain barrier in multiple sclerosis

Takahashi

Maeda

Sano

et al. 2017

Clinical & Exp Neuroim

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Objectives The active form of vitamin D, 1a, 2 D 3 ), is reported to have protective effects for multiple sclerosis (MS), but the precise mechanisms of this effect on MS remain unclear. We hypothesized that 1a,25-(OH) 2 D 3 has protective effects on the blood-brain barrier (BBB) in MS. Methods The expression of vitamin D receptor in a human brain microvascular endothelial cell line (HBMEC) was examined. The effects of 1a,25-(OH) 2 D 3 on HBMEC after stimulation with tumor necrosis factor-a were observed. In addition, we assessed the effects of sera from MS patients, including those in the acute and stable phase of relapse-remitting MS or secondary progressive MS, on the BBB property in the presence or absence of 1a,25-(OH) 2 D 3 . Results HBMEC were found to express the vitamin D receptor at both the mRNA and protein level. Pretreatment of HBMEC with 1a,25-(OH) 2 D 3 attenuated the decrease of zonula occludens-1 and claudin-5, and the increase of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor-a. In addition, nuclear factor kappa B activation mediated by tumor necrosis factor-a was decreased after incubation with the activated vitamin D. Furthermore, incubation with 1a,25-(OH) 2 D 3 attenuated the increase of vascular cell adhesion molecule-1 and anti-phospho-nuclear factor kappa B in HBMEC after exposure to sera from patients with relapse-remitting MS and secondary progressive MS, and restored the decrease of zonula occludens-1 and claudin-5 in HBMEC after incubation with sera from the acute phase of relapse-remitting MS patients. Conclusions Treatment with 1a,25-(OH) 2 D 3 prevents BBB disruption caused by both relapse-remitting MS and secondary progressive MS sera through upregulation of tight junction proteins and downregulation of cell adhesion molecules in HBMEC, suggesting that 1a,25-(OH) 2 D 3 might have the direct protective effects on the fragile BBB in MS patients.

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1,25‐Dihydroxyvitamin D₃ inhibits tumor necrosis factor‐α‐induced adhesion molecule expression in endothelial cells

Cited by 81 publications

References 44 publications

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease

A new role for vitamin D receptor activation in chronic kidney disease

Active form of vitamin D directly protects the blood–brain barrier in multiple sclerosis

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1,25‐Dihydroxyvitamin D3 inhibits tumor necrosis factor‐α‐induced adhesion molecule expression in endothelial cells

Cited by 81 publications

References 44 publications

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease

The effects of vitamin D repletion on endothelial function and inflammation in patients with coronary artery disease

A new role for vitamin D receptor activation in chronic kidney disease

Active form of vitamin D directly protects the blood–brain barrier in multiple sclerosis

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1,25‐Dihydroxyvitamin D₃ inhibits tumor necrosis factor‐α‐induced adhesion molecule expression in endothelial cells