PXD038066

PXD038066 is an original dataset announced via ProteomeXchange.

Title	Sarcomeric Proteoform Landscape in Ischemic Cardiomyopathy Defined by Top-down Proteomics
Description	In ischemic cardiomyopathy (ICM), left ventricular systolic dysfunction leads to reduced blood flow and oxygen supply to the heart. Alterations in sarcomeric protein function and expression play prominent roles in the onset and progression of cardiomyopathies; however, the molecular mechanisms underlying ICM remain poorly defined. Herein, we have implemented a top-down liquid chromatography (LC)-mass spectrometry (MS)-based proteomics method for the simultaneous quantification of sarcomeric protein expression and modifications in non-failing donor (n = 16) compared to end-stage failing ICM (n = 16) human cardiac tissues. Our top-down proteomics platform provided a “bird’s eye view” of proteoform families with high mass accuracy and reproducibility. In addition, quantification of post-translational modifications (PTMs) and expression reveal significant changes in various sarcomeric proteins extracted from ICM tissues. Changes include altered phosphorylation and expression of cardiac troponin I (cTnI) and enigma homolog 2 (ENH2) as well as a marked increase in muscle LIM protein (MLP) and calsarcin-1 phosphorylation in ICM hearts. Our results imply that the contractile apparatus of the sarcomere is severely dysregulated during ICM. Thus, this study is the first to uncover significant molecular changes to multiple sarcomeric proteins in end-stage ischemic heart failure patients using LC-MS-based top-down proteomics.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:33:38.588.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Emily Chapman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-09 10:32:42	ID requested
1	2023-02-20 15:35:51	announced
⏵ 2	2023-11-14 08:33:39	announced	2023-11-14: Updated project metadata.

Chapman EA, Aballo TJ, Melby JA, Zhou T, Price SJ, Rossler KJ, Lei I, Tang PC, Ge Y, Defining the Sarcomeric Proteoform Landscape in Ischemic Cardiomyopathy by Top-Down Proteomics. J Proteome Res, 22(3):931-941(2023) [pubmed]

ProteomeXchange project tag: Cardiovascular (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: ischemic cardiomyopathy, top-down proteomics, sarcomere, Z-disk proteins, myofilament proteins, quantitative proteomics, human heart proteomics

Ying Ge
contact affiliation	Professor, Department of Cell and Regenerative Biology Professor, Department of Chemistry Director of Mass Spectrometry Human Proteomics Program School of Medicine and Public Health University of Wisconsin-Madison
contact email	ying.ge@wisc.edu
lab head
Emily Chapman
contact affiliation	University of Wisconsin - Madison
contact email	eachapman2@wisc.edu
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/2023/02/PXD038066

PRIDE project URI

• PRIDE
  1. PXD038066
     1. Label: PRIDE project
     2. Name: Sarcomeric Proteoform Landscape in Ischemic Cardiomyopathy Defined by Top-down Proteomics