Evidence map›Paper›PMID 40858841›Full record

ArticleNature cardiovascular research2025

Inhibition of proprotein convertase SKI-1 prevents blood vessel alteration after stroke.

Alireza P Shabanzadeh, Dene Ringuette, Michal Syonov, Qisi Wu, Nardos G Tassew, Eric K Mun, Autumn Meek, Starlee Lively, Samuel E Suntharalingham, Mia Mojica and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

23 authors.

Alireza P ShabanzadehKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-3585-7912
Dene RinguetteKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-4567-8109
Michal SyonovKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0009-0009-0896-2347
Qisi WuDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Nardos G TassewKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Eric K MunKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Autumn MeekKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Starlee LivelyKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-0655-535X
Samuel E SuntharalinghamKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Mia MojicaSlaight Family Centre for Advanced MRI, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
Leonardo OlijnykKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Beiping QiangMcEwen Stem Cell Institute, University of Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-2482-3354
Warren D FoltzSTTARR Innovation Centre, Department of Radiation Oncology, University Health Network, Toronto, Ontario, Canada.
Mark ReedKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Ignace MoyaKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Carla BrownKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Jinzhou FengDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xinyue QinDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Pavan Sudheer AkulaKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Thomas WälchliKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Peter L CarlenKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Paula Alcaide-LeonDivision of Neuroradiology, Joint Department of Medical Imaging, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Philippe P MonnierKrembil Research Institute, University Health Network, Toronto, Ontario, Canada. pmonnier@uhnres.utoronto.ca.ORCID http://orcid.org/0000-0002-6221-4130

Funding

Heart and Stroke Foundation of Canada (Heart and Stroke Foundation) G240038139
6 · The paper itself

Abstract

Neutralizing factors involved in blood vessel dysfunction offer a promising strategy for stroke recovery. Many extracellular proteins need enzymatic activation to function, and blocking this activation is an untapped approach to restoring vessel integrity. Here we demonstrate that inhibition of the extracellular protease SKI-1 with PF-429242 restores blood vessel integrity and promotes functional recovery in both large and small animal models for stroke. Single-cell mRNA sequencing identified molecular signatures suggesting that PF-429242 restores the expression of genes involved in vessel integrity in endothelial cells. Moreover, we identify a mechanism whereby RGMa cleavage by SKI-1 is required for RGMa to interact with Neogenin and alter vessel integrity. Either preventing RGMa cleavage or deleting Neogenin on endothelial cells reduced blood vessel dysfunction, increased tissue preservation and restored brain function after stroke. This work identifies a much-needed therapeutic strategy that restores blood vessel integrity and functionality, showing efficacy in large and small animals.

Indexed as

Endothelial CellsInfarction, Middle Cerebral ArteryAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLMice, KnockoutNerve Tissue ProteinsProprotein ConvertasesRecovery of FunctionSerine Endopeptidasesmembrane-bound transcription factor peptidase, site 1Nerve Tissue ProteinsProprotein ConvertasesSerine Endopeptidases

Identifiers

PMID40858841
PMCPMC12436164

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.