Cartland, Siân P. and Patil, Manisha S. and Kelland, Elaina and Le, Natalie and Boccanfuso, Lauren and Stanley, Christopher P. and Cholan, Pradeep Manuneedhi and Dona, Malathi I. and Patrick, Ralph and McGrath, Jordan and Su, Qian Peter and Alwis, Imala and Ganss, Ruth and Powell, Joseph E. and Harvey, Richard P. and Pinto, Alexander R. and Griffith, Thomas S. and Loa, Jacky and Aitken, Sarah J. and Robinson, David A. and Patel, Sanjay and Kavurma, Mary M. (2024) The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL. Science Advances, 10 (40). ISSN 2375-2548
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 30 Dec 2024 04:38 |
| Last Modified: | 30 Dec 2024 04:38 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1601 |
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