Evidence map›Paper›PMID 36860338›Full record

ArticleFrontiers in medicine2023

The loss of glycocalyx integrity impairs complement factor H binding and contributes to cyclosporine-induced endothelial cell injury.

Chia Wei Teoh, Magdalena Riedl Khursigara, Carolina G Ortiz-Sandoval, Jee Woo Park, Jun Li, Arlette Bohorquez-Hernandez, Valentina Bruno, Emily E Bowen, Spencer A Freeman, Lisa A Robinson and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 17 citations in OpenAlex.

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  10. Post-transplant Thrombotic Microangiopathy.Journal of the American Society of Nephrology : JASN · 2025
    Review
  11. Article
  12. Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
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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

11 authors at 3 institutions in 3 countries.

Chia Wei TeohDivision of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Magdalena Riedl KhursigaraDivision of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Carolina G Ortiz-SandovalCell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Jee Woo ParkCell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Jun LiCell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Arlette Bohorquez-HernandezCell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Valentina BrunoDivision of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Emily E BowenBristol Renal, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
Spencer A FreemanCell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Lisa A RobinsonDivision of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Christoph LichtDivision of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Hospital for Sick Children · CAUniversity of Toronto · CAUniversity of Bristol · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Calcineurin inhibitors (CNIs) are associated with nephrotoxicity, endothelial cell dysfunction, and thrombotic microangiopathy (TMA). Evolving evidence suggests an important role for complement dysregulation in the pathogenesis of CNI-induced TMA. However, the exact mechanism(s) of CNI-induced TMA remain(s) unknown. Methods: Using blood outgrowth endothelial cells (BOECs) from healthy donors, we evaluated the effects of cyclosporine on endothelial cell integrity. Specifically, we determined complement activation (C3c and C9) and regulation (CD46, CD55, CD59, and complement factor H [CFH] deposition) as these occurred on the endothelial cell surface membrane and glycocalyx. Results: We found that exposing the endothelium to cyclosporine resulted in a dose- and time-dependent enhancement of complement deposition and cytotoxicity. We, therefore, employed flow cytometry, Western blotting/CFH cofactor assays, and immunofluorescence imaging to determine the expression of complement regulators and the functional activity and localization of CFH. Notably, while cyclosporine led to the upregulation of complement regulators CD46, CD55, and CD59 on the endothelial cell surface, it also diminished the endothelial cell glycocalyx through the shedding of heparan sulfate side chains. The weakened endothelial cell glycocalyx resulted in decreased CFH surface binding and surface cofactor activity. Conclusion: Our findings confirm a role for complement in cyclosporine-induced endothelial injury and suggest that decreased glycocalyx density, induced by cyclosporine, is a mechanism that leads to complement alternative pathway dysregulation

Indexed as

alternative pathwaycalcineurin inhibitorscomplementcyclosporineendotheliumheparan sulfateproteoglycansthrombotic microangiopathy

Identifiers

PMID36860338
PMCPMC9968885
OpenAlexW4320495745

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.