PXD025096

PXD025096 is an original dataset announced via ProteomeXchange.

Title	Integration of functional imaging, cytometry and unbiased proteomics reveals new features of endothelial-to-mesenchymal transition in ischemic mitral valve regurgitation in human patients
Description	Background: Following myocardial infarction, mitral regurgitation (MR) is a common complication. Previous animal studies demonstrated the association of endothelial-to-mesenchymal transition (EndMT) with mitral valve (MV) remodeling. Nevertheless, little is known about how MV tissue responds to ischemic heart changes in humans. Methods: MVs were obtained by the Cardiothoracic Surgical Trials Network from 17 patients with ischemic mitral regurgitation (IMR). Echo-doppler imaging assessed MV function at time of resection. Cryosections of MVs were analyzed using a multi-faceted histology and immunofluorescence examination of cell populations. MVs were further analyzed using unbiased label-free proteomics. Echo-Doppler imaging, histo-cytometry measures and proteomic analysis were then integrated. Results: MVs from patients with greater MR exhibited proteomic changes associated with proteolysis-, inflammatory- and oxidative stress-related processes compared to MVs with less MR. Cryosections of MVs from patients with IMR displayed activated valvular interstitial cells (aVICs) and double positive CD31+ αSMA+ cells, a hallmark of EndMT. Univariable and multivariable association with echocardiography measures revealed a positive correlation of MR severity with both cellular and geometric changes (e.g., aVICs, EndMT, leaflet thickness, leaflet tenting). Finally, proteomic changes associated with EndMT showed gene-ontology enrichment in vesicle-, inflammatory- and oxidative stress-related processes. This discovery approach indicated new candidate proteins associated with EndMT regulation in IMR. Conclusion: We describe an atypical cellular composition and distinctive proteome of human MVs from patients with IMR, which highlighted new candidate proteins implicated in EndMT-related processes, associated with maladaptive MV fibrotic remodeling.
HostingRepository	PRIDE
AnnounceDate	2021-08-13
AnnouncementXML	Submission_2021-08-12_21:53:54.243.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025096
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Adrien Lupieri
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-30 02:44:21	ID requested
⏵ 1	2021-08-12 21:53:54	announced

Dataset with its publication pending

submitter keyword: Human, Ischemic mitral regurgitation (IMR), mitral valve (MV), endothelial-to-mesenchymal transition (EndMT), Echocardiography, Histo-cytometry, Proteomic

Elena Aikawa
contact affiliation	Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
contact email	eaikawa@bwh.harvard.edu
lab head
Adrien Lupieri
contact affiliation	Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA
contact email	adrien.lupieri@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025096
     1. Label: PRIDE project
     2. Name: Integration of functional imaging, cytometry and unbiased proteomics reveals new features of endothelial-to-mesenchymal transition in ischemic mitral valve regurgitation in human patients