Evidence map›Paper›PMID 40069829›Full record

ArticleJournal of translational medicine2025

The FKBPL-based therapeutic peptide, AD-01, protects the endothelium from hypoxia-induced damage by stabilising hypoxia inducible factor-α and inflammation.

Sahar Ghorbanpour, Siân Peta Cartland, Hao Chen, Sanchit Seth, Rupert C Ecker, Claire Richards, Dunja Aksentijevic, Matthew P Padula, Louise Cole, Majid Ebrahimi Warkiani and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Evaluating oxidative stress targeting treatments inFrontiers in cell and developmental biology · 2025
    Article
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

12 authors.

Sahar GhorbanpourSchool of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Siân Peta CartlandHeart Research Institute, The University of Sydney, Sydney, NSW, Australia.
Hao ChenSchool of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Sanchit SethSchool of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
Rupert C EckerSchool of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
Claire RichardsSchool of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Dunja AksentijevicCentre for Biochemical Pharmacology, School of Medicine and Dentistry, William Harvey Research Institute, Barts and the London, Queen Mary University of London, London, UK.
Matthew P PadulaSchool of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Louise ColeThe Australian Institute for Microbiology and Infection (AIMI), Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Majid Ebrahimi WarkianiSchool of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW, Australia.
Mary Meltem KavurmaHeart Research Institute, The University of Sydney, Sydney, NSW, Australia.
Lana McClementsSchool of Life Sciences & Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia. lana.mcclements@uts.edu.au.ORCID 0000-0002-4911-1014

Funding

National Heart Foundation of Australia 106628
6 · The paper itself

Abstract

backgroundEndothelial dysfunction is a hallmark feature of cardiovascular disease (CVD), yet the underlying mechanisms are still poorly understood. This has impeded the development of effective therapies, particularly for peripheral artery disease. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are crucial negative regulators of angiogenesis, however their roles in CVD are unknown. In this study, we aimed to elucidate the FKBPL-mediated mechanisms involved in regulating endothelial dysfunction induced by hypoxia or inflammation, and to determine whether AD-01 can effectively restore endothelial function under these conditions.

methodsHindlimb ischemia was induced in mice by ligating the proximal and distal ends of the right femoral artery, and, after three days, the gastrocnemius muscle was collected for immunofluorescence staining, and RNA extraction. A 3D in vitro microfluidics model was developed to determine the endothelial cell migration and impact of FKBPL following treatments with: (i) 24 µM FKBPL targeted siRNA, (ii) 1 mM hypoxia inducible factor (HIF-1)α activator (DMOG), (iii) 50% (v/v) macrophage conditioned media (MCM), ± 100 nM AD-01. Unbiased, untargeted proteomic analysis was conducted via LC-MS/MS to identify protein targets of AD-01.

resultsFKBPL expression is substantially downregulated in mice after hindlimb ischemia (p < 0.05, protein; p < 0.001, mRNA), correlating with increased neovascularization and altered vascular adhesion molecule expression. In our real-time advanced 3D microfluidics model, hypoxia suppressed FKBPL (p < 0.05) and VE-cadherin (p < 0.001) expression, leading to increased endothelial cell number and migration (p < 0.001), which was restored by AD-01 treatment (p < 0.01). Under inflammatory conditions, FKBPL (p < 0.01) and HIF-1α (p < 0.05) expression was elevated, correlating with increased endothelial cell migration (p < 0.05). Unlike hypoxia, AD-01 did not influence endothelial cell migration under inflammatory conditions, but normalized FKBPL (p < 0.001), HIF-1α (p < 0.05) and CD31 (P < 0.05), expression, in 3D microfluidic cell culture. Proteomic analysis revealed that AD-01 treatment in hypoxia enhanced the abundance of tissue remodelling and vascular integrity proteins including collagen alpha-1(XIX) chain and junctional cadherin associated-5 (JCAD) proteins.

conclusionsFKBPL represents an important novel mechanism in hypoxia and inflammation-induced angiogenesis. The FKBPL-based therapeutic peptide, AD-01, could be a viable treatment option for CVD-related endothelial cell dysfunction.

Indexed as

Endothelium, VascularHypoxiaHypoxia-Inducible Factor 1, alpha SubunitInflammationPeptidesProtective AgentsAnimalsCell HypoxiaCell MovementEndothelial CellsHindlimbHumansHuman Umbilical Vein Endothelial CellsIschemiaMacrophagesMaleHypoxia-Inducible Factor 1, alpha SubunitPeptidesProtective AgentsAngiogenesisEndothelial dysfunctionFKBPLHypoxiaInflammationMicrofluidics

Identifiers

PMID40069829
PMCPMC11895374

What OpenQuestion holds

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LicenceCC BY
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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.