PXD055391

PXD055391 is an original dataset announced via ProteomeXchange.

Title	Cellular and extracellular proteomic profiling of paradoxical low-flow lowgradient aortic stenosis myocardium
Description	Aims: Patients with severe aortic stenosis (AS), low transvalvular flow (LF) and low gradient (LG) with normal ejection fraction (EF)are referred to as paradoxical LF-LG AS (PLF-LG). PLF-LG patients develop more advanced heart failure symptoms and have a worse prognosis than patients with normal EF and high-gradient AS (NEF-HG). Despite its clinical relevance, the mechanisms underlying PLF-LG are still poorly understood. Methods: Left ventricular (LV) myocardial biopsies of PLF-LG (n=5) and NEF-HG patients (n=6), obtained during transcatheter aortic valve implantation, were analyzed by LC-MS/MS after sequential extraction of cellular and extracellular matrix (ECM) proteins using a three-step extraction method.Results: 73 cellular proteins were differentially abundant between the 2 groups. Among these, a network of proteins related to muscle contraction and arrhythmogenic cardiomyopathy (e.g. cTnI, FKBP1A and CACNA2D1) was found in PLF-LG. Extracellularly, upregulated proteins in PLF-LG were related to ATP synthesis and oxidative phosphorylation (e.g. ATP5PF, COX5B and UQCRB). Interestingly, we observed a 1.3-fold increase in cyclophilin A (CyPA), proinflammatory cytokine, in the extracellular extracts of PLF-LG AS patients (p<0.05).LG AS LV sections along with an increase in its receptor, CD147, compared to the NEF-HG AS patients. Levels of core ECM proteins, namely collagens and proteoglycans, were comparable between groups.Our study pinpointed novel candidates and processes with potential relevance in the pathophysiology of PLF-LG. The role of CyPA in particular warrants further investigation.
HostingRepository	PRIDE
AnnounceDate	2024-08-30
AnnouncementXML	Submission_2024-08-30_08:16:55.250.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD055391
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	XIAOKE YIN
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; (18)O labeled deglycosylated asparagine; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-30 07:43:20	ID requested
⏵ 1	2024-08-30 08:16:55	announced

10.3389/FCVM.2024.1398114;

10.6019/PXD055391;

submitter keyword: Myocardial biopsies, Transcatheter aortic valve implantation (TAVI), Cellular and extracellular matrix proteomics, Normal ejection fraction highgradient aortic stenosis,paradoxical low-flow low-gradient aortic stenosis

Prof Manuel Mayr
contact affiliation	National Heart and Lung Institute, Imperial College London, London, UK
contact email	m.mayr@imperial.ac.uk
lab head
XIAOKE YIN
contact affiliation	National Heart and Lung Institute, Faculty of Medicine, Imperial College London
contact email	xiaoke.yin@imperial.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055391
     1. Label: PRIDE project
     2. Name: Cellular and extracellular proteomic profiling of paradoxical low-flow lowgradient aortic stenosis myocardium