Evidence map›Paper›PMID 35050236›Full record

ArticleJournal of cardiovascular development and disease2022

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

Giovanni Cimmino, Stefano Conte, Mariarosaria Morello, Grazia Pellegrino, Laura Marra, Andrea Morello, Giuseppe Nicoletti, Gennaro De Rosa, Paolo Golino, Plinio Cirillo

Open access · goldAbstract read
In one paragraph

Article in Journal of cardiovascular development and disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.

  1. Pooled it
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  6. Computational Modeling of Pro-inflammatory Cytokine-Enhanced Blood Coagulation.Computational and structural biotechnology journal · 2026
    Article
  7. Vitamin D and Brain Health.Advances in experimental medicine and biology · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Giovanni CimminoDepartment of Translational Medical Sciences, Section of Cardiology, University of Campania "Luigi Vanvitelli", 80131 Naples, Italy.ORCID 0000-0002-3802-7052
Stefano ConteDepartment of Translational Medical Sciences, Section of Lung Disease, University of Campania "Luigi Vanvitelli", 80131 Naples, Italy.
Mariarosaria MorelloDepartment of Advanced Biomedical Sciences, Section of Cardiology, University of Naples "Federico II", 80131 Naples, Italy.
Grazia PellegrinoDepartment of Woman, Child and General and Specialized Surgery, Section of Anesthesiology, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Laura MarraDepartment of Cell Biology and Biotherapy Research, Istituto Nazionale Tumori IRCCS-Fondazione G. Pascale, 80131 Naples, Italy.
Andrea MorelloBiochemical Unit, A. S. Re. M. (Azienda Sanitaria Regionale del Molise), Antonio Cardarelli Hospital, 86100 Campobasso, Italy.
Giuseppe NicolettiDepartment of Advanced Biomedical Sciences, Section of Cardiology, University of Naples "Federico II", 80131 Naples, Italy.
Gennaro De RosaDepartment of Advanced Biomedical Sciences, Section of Cardiology, University of Naples "Federico II", 80131 Naples, Italy.ORCID 0000-0002-1210-1269
Paolo GolinoDepartment of Translational Medical Sciences, Section of Cardiology, University of Campania "Luigi Vanvitelli", 80131 Naples, Italy.
Plinio CirilloDepartment of Advanced Biomedical Sciences, Section of Cardiology, University of Naples "Federico II", 80131 Naples, Italy.ORCID 0000-0001-7818-4952
University of Campania "Luigi Vanvitelli" · ITUniversity of Naples Federico II · ITIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale" · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThrombosis 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.

methodsHUVEC 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.

resultsVitD 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.

conclusionsIL-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.

Indexed as

atherothrombosisCOVID-19IL-6tissue factorvitamin D

Identifiers

PMID35050236
PMCPMC8781542
OpenAlexW4206778351

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.