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PXD021858

PXD021858 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleApoC-III is a novel inducer of human valvular calcification
DescriptionPharmacological interventions to treat valvular calcification are not currently part of clinical guidelines. Low-density lipoprotein lowering therapies to treat calcific aortic valve disease (CAVD) failed in clinical trials. However, apolipoproteins are known promotors of atherosclerosis and may play a role in CAVD pathogenesis beyond their lipid-binding capabilities. Lipoprotein particles carry oxidized lipids that promote valvular disease, but whether apolipoproteins themselves possess pathogenic properties in CAVD is less clear. We assessed 12 apolipoproteins in non-fibrotic/non-calcific (NF/NC), fibrotic (F) and calcific (C) aortic valve tissues by proteomics and immunohistochemistry and evaluated effects of enriched apolipoproteins on calcification. Eight apolipoproteins (apoA-I, apoA-II, apoA-IV, apoB, apoC-III, apoD, apoL-I and apoM) were enriched in the C vs. NF/NC tissues. Apo(a), apoB, apoC-III, apoE and apoJ colocalized with the disease-prone fibrosa and calcific regions on histological sections. Circulating apoC-III on lipoprotein(a) was identified as a potential biomarker of aortic stenosis incidence and progression, but whether apoC-III also contributes to CAVD is unknown. ApoC-III was increased in F and C tissues and observed within the calcification-prone fibrosa layer as well as around calcification and induced calcification in primary human valvular cell cultures via a mitochondrial dysfunction/inflammation-mediated calcification pathway. This study provides the first assessment of a broad array of apolipoproteins in CAVD tissues, demonstrates that specific apolipoproteins associate with valvular calcification, and implicates apoC-III as an active, modifiable driver of CAVD beyond its potential role as a biomarker.
HostingRepositoryPRIDE
AnnounceDate2020-12-14
AnnouncementXMLSubmission_2020-12-14_00:07:23.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSasha Singh
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-10-06 01:20:22ID requested
12020-12-14 00:07:23announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: calcific aortic valve disease
valvular interstitial cells
fibrosis
lipids
apoC-III
Contact List
Elena Aikawa
contact affiliationCenter for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
contact emaileaikawa@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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