Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression.
abdominal aortic aneurysm
cardiovascular disease
inflammation
translational research
tumor necrosis factor inhibitor
vascular inflammation
Journal
Frontiers in cardiovascular medicine
ISSN: 2297-055X
Titre abrégé: Front Cardiovasc Med
Pays: Switzerland
ID NLM: 101653388
Informations de publication
Date de publication:
2022
2022
Historique:
received:
12
05
2022
accepted:
08
08
2022
entrez:
3
10
2022
pubmed:
4
10
2022
medline:
4
10
2022
Statut:
epublish
Résumé
Tumor necrosis factor (TNF) is pathologically elevated in human abdominal aortic aneurysms (AAA). Non-selective TNF inhibition-based therapeutics are approved for human use but have been linked to several side effects. Compounds that target the proinflammatory soluble form of TNF (solTNF) but preserve the immunomodulatory capabilities of the transmembrane form of TNF (tmTNF) may prevent these side effects. We hypothesize that inhibition of solTNF signaling prevents AAA expansion. The effect of the selective solTNF inhibitor, XPro1595, and the non-selective TNF inhibitor, Etanercept (ETN) was examined in porcine pancreatic elastase (PPE) induced AAA mice, and findings with XPro1595 was confirmed in angiotensin II (ANGII) induced AAA in hyperlipidemic apolipoprotein E ( XPro1595 treatment significantly reduced AAA expansion in both models, and a similar trend ( In conclusion, selective inhibition of solTNF signaling reduced aneurysm expansion in mice, supporting its potential as an attractive treatment option for AAA patients.
Sections du résumé
Background
UNASSIGNED
Tumor necrosis factor (TNF) is pathologically elevated in human abdominal aortic aneurysms (AAA). Non-selective TNF inhibition-based therapeutics are approved for human use but have been linked to several side effects. Compounds that target the proinflammatory soluble form of TNF (solTNF) but preserve the immunomodulatory capabilities of the transmembrane form of TNF (tmTNF) may prevent these side effects. We hypothesize that inhibition of solTNF signaling prevents AAA expansion.
Methods
UNASSIGNED
The effect of the selective solTNF inhibitor, XPro1595, and the non-selective TNF inhibitor, Etanercept (ETN) was examined in porcine pancreatic elastase (PPE) induced AAA mice, and findings with XPro1595 was confirmed in angiotensin II (ANGII) induced AAA in hyperlipidemic apolipoprotein E (
Results
UNASSIGNED
XPro1595 treatment significantly reduced AAA expansion in both models, and a similar trend (
Conclusion
UNASSIGNED
In conclusion, selective inhibition of solTNF signaling reduced aneurysm expansion in mice, supporting its potential as an attractive treatment option for AAA patients.
Identifiants
pubmed: 36186984
doi: 10.3389/fcvm.2022.942342
pmc: PMC9523116
doi:
Types de publication
Journal Article
Langues
eng
Pagination
942342Informations de copyright
Copyright © 2022 Griepke, Grupe, Lindholt, Fuglsang, Steffensen, Beck, Larsen, Bang-Møller, Overgaard, Rasmussen, Lambertsen and Stubbe.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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