The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.

Cartland, SP; Patil, MS; Kelland, E; Le, N; Boccanfuso, L; Stanley, CP; Cholan, PM; Dona, MI; Patrick, R; McGrath, J; Su, QP; Alwis, I; Ganss, R; Powell, JE; Harvey, RP; Pinto, AR; Griffith, TS; Loa, J; Aitken, SJ; Robinson, DA; Patel, S; Kavurma, MM

The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.

Cartland, SP Patil, MS Kelland, E Le, N Boccanfuso, L Stanley, CP Cholan, PM Dona, MI Patrick, R McGrath, J Su, QP Alwis, I Ganss, R Powell, JE Harvey, RP Pinto, AR Griffith, TS Loa, J Aitken, SJ Robinson, DA Patel, S Kavurma, MM

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Publisher:: AMER ASSOC ADVANCEMENT SCIENCE
Publication Type:: Journal Article
Citation:: Sci Adv, 2024, 10, (40), pp. eadn8760
Issue Date:: 2024-10-04

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Field	Value	Language
dc.contributor.author	Cartland, SP
dc.contributor.author	Patil, MS
dc.contributor.author	Kelland, E
dc.contributor.author	Le, N
dc.contributor.author	Boccanfuso, L
dc.contributor.author	Stanley, CP
dc.contributor.author	Cholan, PM
dc.contributor.author	Dona, MI
dc.contributor.author	Patrick, R
dc.contributor.author	McGrath, J
dc.contributor.author	Su, QP
dc.contributor.author	Alwis, I
dc.contributor.author	Ganss, R
dc.contributor.author	Powell, JE
dc.contributor.author	Harvey, RP
dc.contributor.author	Pinto, AR
dc.contributor.author	Griffith, TS
dc.contributor.author	Loa, J
dc.contributor.author	Aitken, SJ
dc.contributor.author	Robinson, DA
dc.contributor.author	Patel, S
dc.contributor.author	Kavurma, MM
dc.date.accessioned	2024-12-02T01:02:13Z
dc.date.available	2024-12-02T01:02:13Z
dc.date.issued	2024-10-04
dc.identifier.citation	Sci Adv, 2024, 10, (40), pp. eadn8760
dc.identifier.issn	2375-2548
dc.identifier.issn	2375-2548
dc.identifier.uri	http://hdl.handle.net/10453/182195
dc.description.abstract	Reversal of ischemia is mediated by neo-angiogenesis requiring endothelial cell (EC) and pericyte interactions to form stable microvascular networks. We describe an unrecognized role for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in potentiating neo-angiogenesis and vessel stabilization. We show that the endothelium is a major source of TRAIL in the healthy circulation compromised in peripheral artery disease (PAD). EC deletion of TRAIL in vivo or in vitro inhibited neo-angiogenesis, pericyte recruitment, and vessel stabilization, resulting in reduced lower-limb blood perfusion with ischemia. Activation of the TRAIL receptor (TRAIL-R) restored blood perfusion and stable blood vessel networks in mice. Proof-of-concept studies showed that Conatumumab, an agonistic TRAIL-R2 antibody, promoted vascular sprouts from explanted patient arteries. Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER ASSOC ADVANCEMENT SCIENCE
dc.relation.ispartof	Sci Adv
dc.relation.isbasedon	10.1126/sciadv.adn8760
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Mice
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Heparin-binding EGF-like Growth Factor
dc.subject.mesh	Ischemia
dc.subject.mesh	Microvessels
dc.subject.mesh	Neovascularization, Physiologic
dc.subject.mesh	Pericytes
dc.subject.mesh	Peripheral Arterial Disease
dc.subject.mesh	Receptors, TNF-Related Apoptosis-Inducing Ligand
dc.subject.mesh	TNF-Related Apoptosis-Inducing Ligand
dc.subject.mesh	Adult
dc.subject.mesh	Female
dc.subject.mesh	Pericytes
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Ischemia
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Neovascularization, Physiologic
dc.subject.mesh	Adult
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	TNF-Related Apoptosis-Inducing Ligand
dc.subject.mesh	Receptors, TNF-Related Apoptosis-Inducing Ligand
dc.subject.mesh	Microvessels
dc.subject.mesh	Peripheral Arterial Disease
dc.subject.mesh	Heparin-binding EGF-like Growth Factor
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Mice
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Heparin-binding EGF-like Growth Factor
dc.subject.mesh	Ischemia
dc.subject.mesh	Microvessels
dc.subject.mesh	Neovascularization, Physiologic
dc.subject.mesh	Pericytes
dc.subject.mesh	Peripheral Arterial Disease
dc.subject.mesh	Receptors, TNF-Related Apoptosis-Inducing Ligand
dc.subject.mesh	TNF-Related Apoptosis-Inducing Ligand
dc.subject.mesh	Adult
dc.subject.mesh	Female
dc.title	The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	United States
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)/Institute of Biomedical Materials and Devices (IBMD) Associate Members
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0/
dc.date.updated	2024-12-02T01:02:04Z
pubs.issue	40
pubs.publication-status	Published
pubs.volume	10
utslib.citation.issue	40

Abstract:

Reversal of ischemia is mediated by neo-angiogenesis requiring endothelial cell (EC) and pericyte interactions to form stable microvascular networks. We describe an unrecognized role for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in potentiating neo-angiogenesis and vessel stabilization. We show that the endothelium is a major source of TRAIL in the healthy circulation compromised in peripheral artery disease (PAD). EC deletion of TRAIL in vivo or in vitro inhibited neo-angiogenesis, pericyte recruitment, and vessel stabilization, resulting in reduced lower-limb blood perfusion with ischemia. Activation of the TRAIL receptor (TRAIL-R) restored blood perfusion and stable blood vessel networks in mice. Proof-of-concept studies showed that Conatumumab, an agonistic TRAIL-R2 antibody, promoted vascular sprouts from explanted patient arteries. Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/182195