PXD025810
PXD025810 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Interventional- and amputation-stage muscle proteomes in the chronically threatened ischemic limb |
Description | Background: Despite improved surgical approaches for chronic limb threatening ischemia (CLTI), amputation rates remain high and contributing tissue-level factors remain unknown. Objective: The purpose of this study was twofold: 1) to identify differences between the healthy adult and CLTI limb muscle proteome, and 2) to identify differences in the limb muscle proteome of CLTI patients prior to surgical intervention or at the time of amputation. Methods: Gastrocnemius muscle was collected from non-ischemic control (n=26) and either pre-interventional surgery (n=10) or at amputation outcome (n=29) CLTI patients. All samples were subjected to isobaric tandem-mass-tag-assisted quantitative proteomics. Results: The mitochondrion was the primary classification of downregulated proteins (>70%) in CLTI limb muscles and paralleled robust functional mitochondrial impairment. Upregulated proteins (>38%) were largely from the extracellular matrix. Across the two independent sites, 39 proteins were downregulated and 20 upregulated uniformly. Pre-interventional CLTI muscles revealed a robust upregulation of mitochondrial proteins but modest functional impairments in fatty acid oxidation as compared with controls. Comparison of pre-intervention and amputation CLTI limb muscles revealed mitochondrial proteome and functional deficits similar to that between amputation and healthy controls. Interestingly, these observed changes occurred despite 50% of the amputation CLTI patients having undergone a prior surgical intervention. Conclusions: The CLTI proteome supports failing mitochondria as a mechanism contributing to amputation outcomes. The signature of pre-intervention CLTI muscle reveals stable mitochondrial protein abundance that is insufficient to uniformly prevent functional impairments. Taken together, our findings support the investigation of mitochondrial functional therapeutics as both adjuvant and independent therapies for CLTI. |
HostingRepository | jPOST |
AnnounceDate | 2022-04-21 |
AnnouncementXML | Submission_2022-09-18_03:04:47.701.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Kelsey Fisher-Wellman |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; TMT6plex reporter+balance reagent N-acylated residue; TMT6plex reporter+balance reagent acylated N-terminal |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2021-05-05 09:44:48 | ID requested | |
1 | 2022-04-21 10:08:12 | announced | |
⏵ 2 | 2022-09-18 03:04:48 | announced | 2022-09-18: Updated FTP location. |
Publication List
Ryan TE, Kim K, Scali ST, Berceli SA, Thome T, Salyers ZR, O'Malley KA, Green TD, Karnekar R, Fisher-Wellman KH, Yamaguchi DJ, McClung JM, Interventional- and amputation-stage muscle proteomes in the chronically threatened ischemic limb. Clin Transl Med, 12(1):e658(2022) [pubmed] |
Keyword List
submitter keyword: peripheral artery disease, vascular disease, metabolism, surgery, TMT10 |
Contact List
Kelsey Fisher-Wellman | |
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lab head | |
Kelsey Fisher-Wellman | |
contact affiliation | East Carolina Diabetes and Obesity Institute |
dataset submitter |
Full Dataset Link List
jPOST dataset URI |
Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST001157/ |