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

Reynolds, John A.; Rosenberg, Avi Z.; Smith, Carolyne K.; Sergeant, Jamie C.; Rice, Gillian I.; Briggs, Tracy A; Bruce, Ian N.; Kaplan, Mariana J.

doi:10.1002/art.39803

Cited by 31 publications

(19 citation statements)

References 16 publications

(21 reference statements)

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“…Ex vivo studies corroborated the possible vitamin D ability of positively enhancing the endothelial repair mechanisms and the global endothelial function [173,175], for example by reducing the NETosis [79]. Studies in experimental models of SLE (MRL/lpr) also showed that lower levels of vitamin D correlated with impaired endothelium-dependent vasodilation and defective neoangiogenesis in agreement with the human findings [176].…”

Section: Interventional Clinical Trialssupporting

confidence: 60%

To Supplement or not to Supplement? The Rationale of Vitamin D Supplementation in Systemic Lupus Erythematosus

Nerviani¹,

Mauro²,

Gilio³

et al. 2018

TORJ

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Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease characterised by abnormal activation of the immune system, chronic inflammation and organ damage. Lupus patients are more prone to be vitamin D deficient. However, current evidence is not conclusive with regards to the role played by vitamin D in SLE development, progression, and clinical manifestations. Objective: Here, we will summarise the current knowledge about vitamin D deficiency prevalence, risk factors, molecular effects, and potential pathogenic role in SLE. We will focus on the link between vitamin D deficiency and lupus clinical manifestations, and on the clinical trials assessing the effects of vitamin D supplementation in SLE. Method: A detailed literature search was performed exploiting the available databases, using “vitamin D and lupus/SLE” as keywords. The relevant interventional trials published over the last decade have been considered and the results are reported here. Conclusion: Several immune cells express vitamin D receptors. Thus, an immunomodulatory role for vitamin D in lupus is plausible. Numerous observational studies have investigated the relationship between vitamin D levels and clinical/serological manifestations of SLE with contrasting results. Negative correlations between vitamin D levels and disease activity, fatigue, renal and cardiovascular disease, and anti-dsDNA titres have been described but not conclusively accepted. In experimental models of lupus, vitamin D supplementation can improve the disease. Interventional trials have assessed the potential therapeutic value of vitamin D in SLE, but further larger studies are needed.

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Section: Interventional Clinical Trialssupporting

confidence: 60%

To Supplement or not to Supplement? The Rationale of Vitamin D Supplementation in Systemic Lupus Erythematosus

Nerviani¹,

Mauro²,

Gilio³

et al. 2018

TORJ

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“…Whether these factors or their interactions will produce injury to the endothelium needs to be studied further in the future [ Table 1 ]. [ 65 66 67 68 69 70 ]…”

Section: R Isk F Actors R mentioning

confidence: 99%

“…Diseases of some other systems can be accompanied by endothelial injury, such as chronic obstructive pulmonary disease,[ 71 72 ] sepsis,[ 73 ] SLE,[ 70 ] obstructive sleep apnea,[ 74 ] end-stage renal disease,[ 75 ] left ventricular hypertrophy,[ 75 ] Blackfoot disease,[ 76 77 ] and type 2 diabetes[ 78 79 ] [ Table 1 ]. It may be that many diseases are connected to endothelial injuries to varying degrees, but uncovering those connections will require tireless scientific efforts.…”

Section: Oncurrency Of R Elated mentioning

confidence: 99%

Common Injuries and Repair Mechanisms in the Endothelial Lining

Meng

Chen

Zhang

et al. 2018

Chinese Medical Journal

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Objective:Endothelial cells (ECs) are important metabolic and endocrinal organs which play a significant role in regulating vascular function. Vascular ECs, located between the blood and vascular tissues, can not only complete the metabolism of blood and interstitial fluid but also synthesize and secrete a variety of biologically active substances to maintain vascular tension and keep a normal flow of blood and long-term patency. Therefore, this article presents a systematic review of common injuries and healing mechanisms for the vascular endothelium.Data Sources:An extensive search in the PubMed database was undertaken, focusing on research published after 2003 with keywords including endothelium, vascular, wounds and injuries, and wound healing.Study Selection:Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize common injury and repair processes of the endothelial lining.Results:Endothelial injury is closely related to the development of multiple cardiovascular and cerebrovascular diseases. However, the mechanism of vascular endothelial injury is not fully understood. Numerous studies have shown that the mechanisms of EC injury mainly involve inflammatory reactions, physical stimulation, chemical poisons, concurrency of related diseases, and molecular changes. Endothelial progenitor cells play an important role during the process of endothelial repair after such injuries. What's more, a variety of restorative cells, changes in cytokines and molecules, chemical drugs, certain RNAs, regulation of blood pressure, and physical fitness training protect the endothelial lining by reducing the inducing factors, inhibiting inflammation and oxidative stress reactions, and delaying endothelial caducity.Conclusions:ECs are always in the process of being damaged. Several therapeutic targets and drugs were seeked to protect the endothelium and promote repair.

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“…Studies have shown that vascular endothelial structure and function damage was the initiating mechanism of atherosclerosis in SLE [ 4 , 5 ]. The essence of vascular dysfunction is the imbalance between vascular injury and vascular repair, which is an important factor leading to target organ damage, such as the heart, brain, and kidney damage, and cardiovascular events [ 6 , 7 ]. Therefore, the repair of vascular endothelial injury is an important measure to effectively prevent and treat SLE atherosclerosis and its complications.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D (1,25-(OH)2D3) Improves Endothelial Progenitor Cells Function via Enhanced NO Secretion in Systemic Lupus Erythematosus

Huang

Liu

Huang

et al. 2020

Cardiology Research and Practice

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It has been proven that vitamin D was decreased and function of circulating endothelial progenitor cells (EPCs) was injured in systemic lupus erythematosus (SLE) patients. However, the effect of vitamin D on the function of EPCs in vitro and its mechanism need further study. Therefore, we investigated whether vitamin D improved the function of EPCs in vitro. The peripheral blood mononuclear cells of the participants were isolated from SLE patients and control subjects and cultured to EPCs. After the EPCs were treated with vitamin D (1,25-(OH)2D3), we evaluated the number, migratory and proliferative activities, and nitric oxide (NO) production of EPCs in vitro and detected vascular endothelial function by flow-mediated dilatation (FMD). We found that vitamin D in a dose-dependent manner improved number and migratory and proliferative activities of EPCs from SLE patients. Additionally, vitamin D upregulated NO production from EPCs in vitro. A significant correlation between the FMD and plasma NO level was found. There was also a correlation between number, migration, and proliferation of EPCs and NO production. Thus, the present findings indicated that vitamin D improved the function of EPCs from SLE patients via NO secretion.

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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

Abstract: These findings indicate that vitamin D deficiency is associated with hampered vascular repair and reduced endothelial function, and may modulate type I interferon responses.

Cited by 31 publications

References 16 publications

To Supplement or not to Supplement? The Rationale of Vitamin D Supplementation in Systemic Lupus Erythematosus

To Supplement or not to Supplement? The Rationale of Vitamin D Supplementation in Systemic Lupus Erythematosus

Common Injuries and Repair Mechanisms in the Endothelial Lining

Vitamin D (1,25-(OH)2D3) Improves Endothelial Progenitor Cells Function via Enhanced NO Secretion in Systemic Lupus Erythematosus

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