Evidence map›Paper›PMID 40836917›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2025

Heparanase 2 Modulates Vascular Permeability via Heparan Sulfate-Dependent Growth Factor Signaling.

Yannic Becker, Sergey Tkachuk, Anne Jörns, Nelli Shushakova, Song Rong, Ahmad Alwakaa, Jan Hegermann, Heiko Schenk, Yulia Kiyan, Hermann Haller

Abstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 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

10 authors.

Yannic BeckerDepartment of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).ORCID 0009-0009-1050-9509
Sergey TkachukDepartment of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).
Anne JörnsInstitute of Clinical Biochemistry, Hannover Medical School, Germany (A.J.).ORCID 0000-0003-0176-972X
Nelli ShushakovaDepartment of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).ORCID 0000-0003-3772-4136
Song RongDepartment of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).ORCID 0000-0001-9985-1515
Ahmad AlwakaaDepartment of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).ORCID 0009-0007-7558-4193
Jan HegermannInstitute for Functional and Applied Anatomy, Hannover Medical School, Germany (J.H.).ORCID 0000-0001-7893-8507
Heiko Schenk *Department of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).ORCID 0000-0003-2693-5712
Yulia Kiyan *Department of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).
Hermann Haller *Department of Nephrology, Hannover Medical School, Germany (Y.B., S.T., N.S., S.R., A.A., H.S., Y.K., H.H.).

Funding

The Maine Biomedical Research Network (INBRE)P20GM103423 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI JAMES A COFFMAN · 2012 to 2026
$60.0M
Understanding the role of thyroid hormone signaling during axolotl limb regenerationP20GM104318 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI DRUMMOND, IAIN A. · 2013 to 2023
$23.0M
NIGMS NIH HHS P20 GM103423NIGMS NIH HHS P20 GM104318
6 · The paper itself

Abstract

backgroundVessel-lining endothelial cells (ECs) rely on heparan sulfate (HS) proteoglycans to regulate vascular permeability and to maintain vascular homeostasis. Hpa2 (heparanase 2) is a little-known, nonenzymatic, HS-binding protein. We hypothesized major functions and thus characterized the role of endogenous Hpa2 in the vertebrate vascular system.

methodsWe use zebrafish larvae as our primary animal model. Hpa2 loss-of-function (LOF) was induced by CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) and morpholino antisense strategies. We assessed vascular permeability, blood vessel architecture, and EC morphology using transgenic zebrafish and transmission electron microscopy. rHpa2 (recombinant heparanase 2) was generated to study the functionality of Hpa2 in endothelial tissue cultures, zebrafish, and mice.

resultsWe detected Hpa2 expression in hepatic tissue and localized Hpa2 protein in the vasculature of zebrafish and mammals. Hpa2 LOF increased zebrafish vascular permeability and altered EC and extracellular matrix morphology. rHpa2 rescued the Hpa2 LOF phenotype. Hpa2 LOF reduced HS levels and caused EC gene expression changes involved in signal transduction. rHpa2 competed with growth factors FGF2 (fibroblast growth factor-2) and VEGFA

conclusionsWe suggest that Hpa2 is a circulating molecule that maintains vascular integrity by regulating vascular HS-dependent growth factor signaling. Our model outlines Hpa2-related vascular function and could indicate therapeutic utilities.

Indexed as

Capillary PermeabilityEndothelial CellsGlucuronidaseHeparan SulfateVascular Endothelial Growth Factor AZebrafish ProteinsAnimalsAnimals, Genetically ModifiedCells, CulturedHeparanaseHumansLiverMiceSignal TransductionZebrafishGlucuronidaseHeparanaseHeparan SulfateVascular Endothelial Growth Factor AVegfaa protein, zebrafishZebrafish Proteinsendothelial cellsheparanaseheparan sulfate proteoglycanshomeostasiszebrafish

Identifiers

PMID40836917
PMCPMC12685291

What Socratic holds

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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.