Vitamin D inhibits Tissue Factor and CAMs expression in oxidized low-density lipoproteins-treated human endothelial cells by modulating NF-κB pathway.

Cimmino, Giovanni; Morello, Andrea; Conte, Stefano; Pellegrino, Grazia; Marra, Laura; Golino, Paolo; Cirillo, Plinio

doi:10.1016/j.ejphar.2020.173422

Cited by 23 publications

(32 citation statements)

References 71 publications

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“…At confluence, cells were starved in serum-free medium for 24 h enriched with VitD (1a,25-dihydroxyvitamin D3, Catalog Number D1530, Sigma-Aldrich, St. Louis, MO, USA; dissolved in ethanol 0.1% following manufacturer's instruction), at final concentration of 10 nM for 1 h, as already reported [18,19], and then incubated with native IL-6 (0.5 ng/mL). LPS-stimulated cells (50 µg/mL) served as positive control and non-VitD treated cells served as negative control.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…LPS-stimulated cells (50 µg/mL) served as positive control and non-VitD treated cells served as negative control. Evaluation of Tissue Factor expression was assessed as previously reported [19] at 1 and 2 h for gene and 6 and 12 h for protein levels. Surface expression and activity were assessed at 6 h. Similarly, ACE2r, Caspase-1 (as main part of the Inflammasome) and CAMs expression were evaluated.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Finally, to verify the effective involvement of VitD receptor (VDR) in the action mechanism of VitD, HUVECs were also treated with VDR antagonist ZK159222 (Bayer Schering Pharma AG, Berlin, Germany). This VDR antagonist was used at the same concentration as VitD (10 nM) as already reported [19]. Expression of TF-mRNA and procoagulant activity were evaluated.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…Tissue Factor gene levels were evaluated in stimulated HUVECs and were assessed at 1 and 2 h as previously described [19]. After stimulation, cells were washed with phosphatebuffered saline (PBS).…”

Section: Tissue Factor Gene and Protein Levels Surface Translocation And Functional Activitymentioning

confidence: 99%

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Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection?

Cimmino

Conte

Morello

et al. 2022

JCDD

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Background: Thrombosis with cardiovascular involvement is a crucial complication in COVID-19 infection. COVID-19 infects the host by the angiotensin converting enzyme-2 receptor (ACE2r), which is expressed in endothelial cells too. Thus, COVID-related thrombotic events might be due to endothelial dysfunction. IL-6 is one of the main cytokines involved in the COVID-19 inflammatory storm. Some evidence indicates that Vitamin D (VitD) has a protective role in COVID-19 patients, but the molecular mechanisms involved are still debated. Thus, we investigated the effect of VitD on Tissue Factor and adhesion molecules (CAMs) in IL-6-stimulated endothelial cells (HUVEC). Moreover, we evaluated levels of the ACE2r gene and proteins. Finally, we studied the modulation of NF-kB and STAT3 pathways. Methods: HUVEC cultivated in VitD-enriched medium were stimulated with IL-6 (0.5 ng/mL). The TF gene (RT-PCR), protein (Western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. Similarly, CAMs soluble values (ELISA) and ACE2r (RT-PCR and Western blot) levels were assessed. NF-kB and STAT3 modulation (Western blot) were also investigated. Results: VitD significantly reduced TF expression at both gene and protein levels as well as TF-procoagulant activity in IL-6-treated HUVEC. Similar effects were observed for CAMs and ACE2r expression. IL-6 modulates these effects by regulating NF-κB and STAT3 pathways. Conclusions: IL-6 induces endothelial dysfunction with TF and CAMs expression via upregulation of ACE2r. VitD prevented these IL-6 deleterious effects. Thus, it might be speculated that this is one of the hypothetical mechanism(s) by which VitD exerts its beneficial effects in COVID-19 infection.

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Section: Experimental Protocolmentioning

confidence: 99%

Section: Experimental Protocolmentioning

confidence: 99%

Section: Experimental Protocolmentioning

confidence: 99%

Section: Tissue Factor Gene and Protein Levels Surface Translocation And Functional Activitymentioning

confidence: 99%

See 2 more Smart Citations

Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection?

Cimmino

Conte

Morello

et al. 2022

JCDD

Self Cite

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“…Treatment of an activated (inflamed) endothelial cell line with VD suppresses gene expression for tissue factors and adhesion molecules. 122 Furthermore, treatment with VD in patients with chronic kidney disease who have endothelial dysfunction with high serum levels of circulating microparticles leads to a significant reduction in the level of microparticles; 123 it has also been found to inhibit microparticle release from a human endothelial cell line after their exposure to oxidative stress. 124 Moreover, supplementing high doses of VD decreases thrombin production in severely VD deficient patients.…”

Section: Effect Of Vitamin D On Platelet Leukocyte Aggregationmentioning

confidence: 99%

A Potential Role of Vitamin D on Platelet Leukocyte Aggregation and Pathological Events in Sepsis: An Updated Review

Alharbi¹

2021

JIR

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Vitamin D deficiency and sepsis are both significant global health problems. Insufficient vitamin D is considered to be a pathogenically relevant factor of sepsis-related deaths; however, a causal relationship has not yet been demonstrated. Recently, vitamin D has been an exciting field of research owing to the identification of vitamin D receptors on many extra skeletal tissues and cells, suggesting an unexpected role on body physiology, beyond its effects on bone homeostasis. However, while the role of vitamin D on bone health is widely understood and has been successfully translated into clinical applications and public health policies, recent evidence supporting its role in other physiological and pathological processes has not been fully established. In sepsis, there is an induction of local intracellular vitamin D activity by most immune cells, including lymphocytes, macrophages, neutrophils, and dendritic cells, as well as vascular endothelial cells, to ensure efficient clearance of infective microorganisms and mediate anti-inflammatory and tolerogenic effects. The literature suggests an association between low vitamin D levels and sepsis, but clinical trials have yielded contradictory results. A greater understanding of this role may improve disease management. This article reviews the available knowledge regarding vitamin D in immune function, emerging literature regarding the association between its deficiency and sepsis, as well as presenting its potential effect on platelet leukocyte aggregations (PLAs), a significant pathology in sepsis. It also summarizes clinical trials involving vitamin D supplementation during critical illness and sepsis and addresses the impact of relevant factors of sepsis pathogenesis on the efficacy of vitamin D supplementation, which could contribute to the reported inconsistencies. Looking ahead, further studies are required to uncover the possible modulatory relationship between vitamin D and sepsis to define better cut-offs for its levels, proper timing of its administration, and the optimum dosage for best management.

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Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

Jodele

Sabulski

2023

American J Hematol

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Over the last decade there have been numerous advances in both the diagnosis and treatment of transplant-associated thrombotic microangiopathy (TA-TMA). These are largely the result of an improved understanding of complement activation in TA-TMA and the ability to prevent end organ injury and death with timely initiation of complementblocking therapies. In this article, we review our current understanding of the pathophysiology of TA-TMA, particularly as it pertains to complement activation, endothelial injury, and clinical management. We then review novel complement-blocking therapies that are currently under investigation for use in TA-TMA, as well as discuss special considerations for complement-blocking therapy in hematopoietic stem cell transplant recipients. Through these reviews we aim to answer or at least provide an educated discussion on the most commonly posed TA-TMA management questions and dilemmas.

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Vitamin D inhibits Tissue Factor and CAMs expression in oxidized low-density lipoproteins-treated human endothelial cells by modulating NF-κB pathway.

Cited by 23 publications

References 71 publications

Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection?

Vitamin D Inhibits IL-6 Pro-Atherothrombotic Effects in Human Endothelial Cells: A Potential Mechanism for Protection against COVID-19 Infection?

A Potential Role of Vitamin D on Platelet Leukocyte Aggregation and Pathological Events in Sepsis: An Updated Review

Reeling in complement in transplant‐associated thrombotic microangiopathy: You're going to need a bigger boat

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