PXD035178

PXD035178 is an original dataset announced via ProteomeXchange.

Title	Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression
Description	Tumor necrosis factor (TNF) is elevated in human abdominal aortic aneurysms (AAA). Non-selective TNF inhibition has been linked to several severe side effects. Compounds that target the proinflammatory soluble TNF (solTNF) while preserving the immunomodulatory capabilities of transmembrane TNF (tmTNF) may prevent such side effects. We hypothesize that inhibition of solTNF signaling by XPro1595 is just as effective as non-selective TNF inhibition by etanercept (ETN) in preventing AAA expansion. The effect of XPro1595 and ETN was examined in porcine pancreatic elastase (PPE) induced AAA mice and findings of XPro1595 was confirmed in Angiotensin II (AngII) induced AAA in hyperlipidemic apolipoprotein E (Apoe) -/- mice. XPro1595 treatment significantly reduced AAA expansion in both models, while a similar trend (p=0.06) was observed in ETN-treated mice using the PPE model. In the PPE aneurysm wall, elastin integrity scores were significantly improved in the XPro1595 group. In the aneurysms, mean TNFR1wasreduced no-significantly (p=0.07) by 50% non-significant after TNF inhibition, but the cellular location in murine AAAs were unaffected and like the localization in human AAAs. Systemic TNF levels were elevated in XPro1595-treated mice, while systemic IL-10 levels were significantly increased after ETN-treatment, while in AngII induced AAA mice systemic TNF and IL5 levels were elevated after XPro1595 treatment. In early AAA development, proteomic analyses revealed that components of the fibrinogen complex were elevated while prostaglandin E2 synthase was down regulated by Xpro1595 (unadjusted p-values). David’s ontology analyses revealed that several pathways including cell matrix adhesion, extracellular space, fibrinogen complex, blood microparticles and glycoproteins were elevated by XPro1595 treatment. In conclusion, selective inhibition of solTNF reduces aneurysm expansion. This supports targeting solTNF as an attractive treatment option for AAA patients.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:27:24.416.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hans Christian Beck
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; deaminated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-08 01:31:38	ID requested
1	2022-10-14 00:14:39	announced
⏵ 2	2023-11-14 08:27:25	announced	2023-11-14: Updated project metadata.

Griepke S, Grupe E, Lindholt JS, Fuglsang EH, Steffensen LB, Beck HC, Larsen MD, Bang-M, ø, ller SK, Overgaard M, Rasmussen LM, Lambertsen KL, Stubbe J, Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression. Front Cardiovasc Med, 9():942342(2022) [pubmed]

submitter keyword: mouse abdominal aorta aneurysm

Hans Christian Beck
contact affiliation	Proteomics Lab, Odense University Hospital, Odense DK
contact email	hans.christian.beck@rsyd.dk
lab head
Hans Christian Beck
contact affiliation	Odense University Hospital, Odense, Denmark
contact email	hans.christian.beck@rsyd.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035178
     1. Label: PRIDE project
     2. Name: Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression