PXD021858 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ApoC-III is a novel inducer of human valvular calcification |
Description | Pharmacological 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. |
HostingRepository | PRIDE |
AnnounceDate | 2020-12-14 |
AnnouncementXML | Submission_2020-12-14_00:07:23.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Sasha Singh |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos; Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-06 01:20:22 | ID requested | |
⏵ 1 | 2020-12-14 00:07:23 | announced | |
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 affiliation | Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA |
contact email | eaikawa@bwh.harvard.edu |
lab head | |
Sasha Singh |
contact affiliation | Brigham and Women's Hospital, Harvard Medical School |
contact email | sasingh@bwh.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021858
- Label: PRIDE project
- Name: ApoC-III is a novel inducer of human valvular calcification