PXD073246

PXD073246 is an original dataset announced via ProteomeXchange.

Title	Proteomic and degradomic signatures of extracellular matrix remodeling in calcific aortic valve
Description	Calcific aortic valve disease (CAVD) is the most common valvular heart disease in older adults, but no medical therapy is currently able to halt or reverse its progression, partly because the molecular mechanisms of valve remodeling remain incompletely understood. Here, we aimed to dissect the extracellular matrix (ECM)-centered mechanisms altered in CAVD by integrating untargeted and targeted proteomics, degradomics, collagen post-translational modification (PTM) mapping, and histology in human aortic valves. We analyzed valvular tissue from patients with severe aortic stenosis (n = 10) and non-stenotic controls (n = 9) using data-independent acquisition (DIA) LC–MS/MS, followed by Gene Ontology enrichment, semi-tryptic peptide profiling, hydroxyproline-focused PTM analysis, Multiple Reaction Monitoring (MRM) validation, and elastin staining. DIA proteomics quantified 1,971 proteins and identified 462 significantly modulated in severe CAVD, revealing a landscape dominated by complement activation, coagulation and fibrinolysis, humoral immune response, and extensive ECM organization and wound-healing programs, alongside down-regulation of biosynthetic and metabolic pathways. A degradomic-like analysis of 1,564 semi-tryptic peptides, filtered to exclude proteins with overall abundance changes, yielded 11 preferential ECM substrates, forming a highly interconnected network enriched in small leucine-rich proteoglycans (decorin, lumican, PRELP), microfibrillar components (fibrillin-1), and collagen VI, with fibrinogen and complement C1s bridging toward the thrombo-inflammatory milieu. Collagen-specific PTM mapping demonstrated a marked increase in hydroxyproline-containing peptides in several fibrillar and non-fibrillar collagen chains, despite largely unchanged or even reduced total collagen abundance, indicating qualitative remodeling with enhanced collagen maturation and potential ECM stiffening rather than simple protein accumulation. Histological assessment using Verhoeff–Van Gieson staining confirmed prominent elastin rarefaction and fragmentation with collagen-rich replacement in stenotic cusps. MRM validation of a focused panel of coagulation, complement, and ECM-related proteins (including F2, F9, F10, C3, KNG1, FGG, KLKB1, ACAN, EMILIN1, and HTRA1) corroborated their up-regulation in diseased valves. Together, these multi-layer data support a model in which CAVD is driven by an ECM-centered, thrombo-inflammatory remodeling process characterized by selective proteolysis of key structural matrix components, collagen PTM dysregulation, and loss of elastin integrity. This integrated “structural–degradomic–PTM” signature may provide a basis for developing tissue and circulating biomarkers of disease activity and for identifying novel targets to modulate matrix remodeling in calcific aortic valve disease.
HostingRepository	PRIDE
AnnounceDate	2026-05-29
AnnouncementXML	Submission_2026-05-29_07:26:31.633.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ilaria iacobucci
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	hydroxylated proline; deamidated residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-19 12:00:40	ID requested
⏵ 1	2026-05-29 07:26:32	announced

Iacobucci I, Monaco V, Lobianco AL, Cipolletta B, Birolo L, Conte M, Myasoedova VA, Valerio V, Poggio P, Parisi V, Monti M, Proteomic and degradomic signatures of extracellular matrix remodeling in calcific aortic valve stenosis. Mol Med, ():(2026) [pubmed]

10.1186/s10020-026-01499-0;

submitter keyword: Aortic valve stenosis, Extracellular matrix remodeling Proteomics,Calcific aortic valve disease, Collagen post-translational modifications

Maria Monti
contact affiliation	University of Naples Federico II and CEINGE Biotecnoloige Avanzate "Franco Salvatore"
contact email	montimar@unina.it
lab head
ilaria iacobucci
contact affiliation	Department of Chemical Sciences, University of Naples Federico II, Naples 80126, Italy CEINGE Advanced Biotechnologies, University of Naples Federico II, Naples 80145, Italy
contact email	iacobucci@ceinge.unina.it
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/2026/05/PXD073246

PRIDE project URI

• PRIDE
  1. PXD073246
     1. Label: PRIDE project
     2. Name: Proteomic and degradomic signatures of extracellular matrix remodeling in calcific aortic valve