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PXD051108

PXD051108 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleADP-ribosylation in experimental atherosclerosis: a potential link between dyslipidemia and inflammation in cardiovascular disease
DescriptionMultimodal inflammation and lipid accumulation are major features of atherosclerosis, a leading cause of death and morbidity worldwide. Our previous study recognized ADP-ribosylation, a post-translational modification, as a novel regulator of macrophage-induced inflammation and atherogenesis.2 Our recent ADP-ribosylome study using an acute inflammation mouse model demonstrated that systemic IFN-gamma administration induced changes to the ADP-ribosylation of lipid-binding and macrophage-associated proteins in the liver and spleen of wild-type mice, respectively. We also identified ADP-ribosylated apolipoproteins A-I and A-II (APOA1, APOA2) in the liver of wild-type mice. In this current study, we investigated the ADP-ribosylome of the atherosclerotic aorta derived from low-density lipoprotein receptor-deficient (Ldlr-/-) mice. Mice were fed a regular chow diet or a high-fat diet (HFD) for 3 or 6 months before harvesting the aorta, liver, and plasma. ADP-ribosylome enrichment from mouse aorta presented several challenges that were overcome by pooling 10 aortae per diet/month group, and applying our unique and recently optimized ion mobility mass spectrometry strategy to increase ADP-ribosyl peptide signals. The increased prevalence of ADP-ribosylated apolipoproteins in both liver and aorta of HFD-fed mice suggests that the liver secreted them as lipoproteins which eventually accumulated in the aorta. In particular, ADP-ribosylation sites predominated the C-terminus of APOA1. As C-terminal helices of APOA1 are important for lipid binding, engagement of ABCA1 in smaller HDL particles, and the interaction of lipid-free APOA1 with macrophages and specific lipid efflux, disturbance in the ADP-ribosylation of this region could impair the protein’s functions.
HostingRepositoryPRIDE
AnnounceDate2025-09-19
AnnouncementXMLSubmission_2025-09-19_08:17:01.571.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD051108
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterSasha Singh
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListadenosine diphosphoribosyl (ADP-ribosyl) modified residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-31 14:58:15ID requested
12025-09-19 08:17:01announced
Publication List
10.1161/ATVBAHA.125.322497;
10.6019/PXD051108;
Keyword List
submitter keyword: Ldlr mice, PTM, aorta, ADP ribosylation, liver, atherosclerose, LC-MS/MS
Contact List
Masanori Aikawa
contact affiliationCardiovascular department, Center for Interdisciplinary Cardiovascular Sciences, BWH, Harvard Medical School
contact emailmaikawa@bwh.harvard.edu
lab head
Sasha Singh
contact affiliationBrigham and Women's Hospital, Harvard Medical School
contact emailsasingh@bwh.harvard.edu
dataset submitter
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Dataset FTP location
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