PXD030857

PXD030857 is an original dataset announced via ProteomeXchange.

Title	Unstable Atherosclerotic Plaque Proteome
Description	The rupture of unstable atherosclerotic plaques, leading to debilitating or fatal thrombotic events, is a major health burden worldwide. Limited understanding as to the molecular drivers of plaque instability and rupture hinders efforts in diagnosis and treatment prior to thrombotic events. Utilising an advanced pre-clinical mouse model (Tandem stenosis (TS) model), which presents human-like unstable atherosclerotic disease, we apply high-end omic methods to characterize the molecular signatures associated with plaque instability in atherosclerotic arteries. Through quantitative proteomic profiling, we depict unique proteome signatures of unstable plaques compared to stable plaques and healthy arteries. Coupled with single-cell RNA-sequencing of leukocytes, we describe the heterodimer complex S100a8/S100a9 as unique to unstable plaque, with neutrophils implicated as the transcriptional drivers of S100a8/a9 expression. We confirm S100a9 expression in human carotid atherosclerotic plaques and we further utilise the TS pre-clinical model to pharmacologically inhibit S100a8/S100a9, resulting in plaque stabilisation. Thus, we establish the TS model as a sophisticated translational tool for the profiling of unstable atherosclerotic plaques and demonstrate that unstable and stable atherosclerosis are highly different disease entities.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:46:46.693.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	david greening
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-10 00:43:33	ID requested
1	2023-05-10 13:35:21	announced
⏵ 2	2023-11-14 08:46:50	announced	2023-11-14: Updated project metadata.

Chen YC, Smith M, Ying YL, Makridakis M, Noonan J, Kanellakis P, Rai A, Salim A, Murphy A, Bobik A, Vlahou A, Greening DW, Peter K, Quantitative proteomic landscape of unstable atherosclerosis identifies molecular signatures and therapeutic targets for plaque stabilization. Commun Biol, 6(1):265(2023) [pubmed]

ProteomeXchange project tag: Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Atherosclerosis, Therapeutic,Mouse, Plaque, Proteome

David Greening
contact affiliation	Baker Heart and Diabetes Institute, Aus
contact email	david.greening@baker.edu.au
lab head
david greening
contact affiliation	Baker Heart and Diabetes Inst.
contact email	david.greening@baker.edu.au
dataset submitter

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.pride.ebi.ac.uk/pride/data/archive/2023/05/PXD030857

PRIDE project URI

• PRIDE
  1. PXD030857
     1. Label: PRIDE project
     2. Name: Unstable Atherosclerotic Plaque Proteome