PXD060147

PXD060147 is an original dataset announced via ProteomeXchange.

Title	Cells from PCSK9D374Y minipigs HFHC and LF/MTPi LC-MS/MS
Description	Positron emission tomography (PET) imaging with the radiolabeled glucose analogue fluorodeoxyglucose (18FDG) is widely used to monitor atherosclerosis in clinical trials, but there is uncertainty regarding the plaque cell types that accumulate FDG and how uptake is regulated. The longstanding view that 18FDG is mainly taken up by macrophages is at odds with human and experimental data, and the impact of disease activity on 18FDG uptake has not been examined directly. To analyze the ability of 18FDG-PET to monitor disease activity, we developed a large-animal model of plaque regression in minipigs with hepatic overexpression of a gain-of-function mutant of proprotein convertase subtilisin kexin type 9 (PCSK9). Atherosclerosis was induced through 12 months of high-fat feeding, and disease activity was then lowered for 3 months by reducing plasma cholesterol with a low-fat diet alone or in combination with microsomal transfer protein inhibition. Plaque regression was evident from reduced lipid content, reduced necrotic core size, and partial resolution of plaque inflammation. These changes were accompanied by lowering of the 18FDG-PET signal to that in non-atherosclerotic control pigs. Single-cell gene expression profiling revealed that the reduction of disease activity in regressing plaques occurred with substantial downregulation versus progressing plaques of genes encoding glycolytic enzymes in SMCs, modulated SMCs, macrophages, and lymphocytes. The ability of 18FDG-PET imaging to monitor atherosclerosis thus reflects the tight link between disease activity and glycolytic activity in all major cell types of minipig atherosclerotic plaque.
HostingRepository	PRIDE
AnnounceDate	2025-07-07
AnnouncementXML	Submission_2025-07-07_05:37:31.360.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David del Rio Aledo
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-24 05:00:50	ID requested
⏵ 1	2025-07-07 05:37:31	announced

Dataset with its publication pending

submitter keyword: minipigs, MTPi, cells, LC-MS/MS

Jesus Vázquez
contact affiliation	Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
contact email	jesus.vazquez@cnic.es
lab head
David del Rio Aledo
contact affiliation	Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC)
contact email	david.delrio@cnic.es
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/2025/07/PXD060147

PRIDE project URI

• PRIDE
  1. PXD060147
     1. Label: PRIDE project
     2. Name: Cells from PCSK9D374Y minipigs HFHC and LF/MTPi LC-MS/MS