Evidence mapPaperPMID 42104263Full record

ArticleMolecular medicine (Cambridge, Mass.)2026

Proteomic and degradomic signatures of extracellular matrix remodeling in calcific aortic valve stenosis.

Ilaria Iacobucci, Vittoria Monaco, Alessia Lubrano Lobianco, Brunella Cipolletta, Leila Birolo, Maddalena Conte, Veronika A Myasoedova, Vincenza Valerio, Paolo Poggio, Valentina Parisi and 1 more

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Ilaria IacobucciDepartment of Chemical Sciences, University of Naples "Federico II", Strada Comunale Cinthia, 21, Naples, 80126, Italy. ilaria.iacobucci@unina.it.
Vittoria MonacoDepartment of Chemical Sciences, University of Naples "Federico II", Strada Comunale Cinthia, 21, Naples, 80126, Italy.
Alessia Lubrano LobiancoDepartment of Chemical Sciences, University of Naples "Federico II", Strada Comunale Cinthia, 21, Naples, 80126, Italy.
Brunella CipollettaDepartment of Chemical Sciences, University of Naples "Federico II", Strada Comunale Cinthia, 21, Naples, 80126, Italy.
Leila BiroloDepartment of Chemical Sciences, University of Naples "Federico II", Strada Comunale Cinthia, 21, Naples, 80126, Italy.
Maddalena ConteDepartment of Translational Medical Sciences, University of Napoli "Federico II", Via Pansini, 5, Naples, 80131, Italy.
Veronika A MyasoedovaApplied Biotechnology in Cardiovascular Inflammation Unit, Centro Cardiologico Monzino IRCCS, Milan, Italy.
Vincenza ValerioApplied Biotechnology in Cardiovascular Inflammation Unit, Centro Cardiologico Monzino IRCCS, Milan, Italy.
Paolo PoggioApplied Biotechnology in Cardiovascular Inflammation Unit, Centro Cardiologico Monzino IRCCS, Milan, Italy. paolo.poggio@cardiologicomonzino.it.
Valentina ParisiDepartment of Translational Medical Sciences, University of Napoli "Federico II", Via Pansini, 5, Naples, 80131, Italy.
Maria MontiDepartment of Chemical Sciences, University of Naples "Federico II", Strada Comunale Cinthia, 21, Naples, 80126, Italy.

Funding

Fondazione Gigi e Pupa Ferrari FPF-14Ministero della Salute Ricerca Finalizzata: GR-2019-1237056
6 · The paper itself

Abstract

backgroundAortic stenosis is a progressive fibro-inflammatory valvular disorder with major clinical burden and no disease-modifying pharmacological therapy. Defining molecular circuits associated with thrombo-inflammatory activation to extracellular matrix remodeling may enable future therapeutic targeting and biomarker development.

methodsHuman aortic valves explanted from patients with severe aortic stenosis and non-stenotic surgical controls (aortic regurgitation) were profiled using a multi-layer mass spectrometry strategy. Global protein changes were quantified by label-free proteomics (data-independent acquisition). Extracellular matrix proteolysis was interrogated using an extracellular matrix-focused semi-tryptic peptide workflow. Collagen qualitative remodeling was assessed by mapping hydroxyproline enrichment. Differential abundance was evaluated using multiple-testing correction (false discovery rate). Selected candidates were validated by targeted multiple reaction monitoring, and elastin integrity was assessed histologically.

resultsWe identified 594 significantly modulated proteins in severe aortic stenosis, with predominant upregulation of complement/coagulation and extracellular matrix-related pathways. Targeted Multiple Reaction Monitoring confirmed key thrombo-inflammatory and matrix-associated candidates. Semi-tryptic profiling revealed a focused extracellular matrix degradomic signature dominated by small leucine-rich proteoglycans (decorin, lumican, PRELP), fibrillin-1, and collagen VI, consistent with preferential proteolytic targeting of structural matrix scaffolds. Histology showed marked elastin fragmentation in stenotic leaflets. Collagen post-translational modification analysis revealed increased hydroxyproline- bearing peptides across selected collagen chains despite minimal changes in total collagen abundance, indicating qualitative remodeling beyond protein accumulation.

conclusionsAn integrated proteomic-degradomic-post-translational modification framework reveals concomitant thrombo-inflammatory activation to matrix breakdown and qualitative collagen remodeling in severe aortic stenosis, highlighting molecular circuits that may inform future biomarker development and therapeutic target discovery.

Indexed as

Aortic ValveAortic Valve StenosisCalcinosisExtracellular MatrixProteomeProteomicsAgedBiomarkersCollagenElastinExtracellular Matrix ProteinsFemaleHumansMaleProteolysisBiomarkersCollagenElastinExtracellular Matrix ProteinsProteomeCalcific aortic valve diseaseCollagen post-translational modificationsComplementDegradomicsExtracellular matrixProteomics

Identifiers

PMID42104263
PMCPMC13321448

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.