PXD002950

PXD002950 is an original dataset announced via ProteomeXchange.

Title	Plasma-derived extracellular vesicles contain predictive biomarkers and potential therapeutic targets for myocardial ischemic injury
Description	Myocardial infarction (MI), an undesirable clinical outcome of coronary artery disease (CAD), triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, which is necessary for myocardial healing. However, when in excess, causes pathological tissue remodeling and eventual heart failure. Timely repression of MI-induced inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains clinically challenging. The well documentation on the ability of EVs to trigger a functional response with the delivery of bioactive cargos carried within, have made them clinically attractive as diagnostic biomarkers and drug vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with (MI) and from control patients with stable angina (NMI). We report, for the first time, the expression proteomics profiling on 252 plasma EV proteins that were modulated with >1.2-fold in myocardial injury. We identified a panel of six strongly up-regulated biomarkers with significant potential for clinical applications; these reflected post-infarct pathways of complement activation (Complement C1q subcomponent subunit A [C1QA], ~3.23-fold change, p = 0.012; Complement C5 [C5], ~1.27-fold change, p = 0.087), lipoprotein metabolism (Apoliporotein D [APOD], ~1.86-fold change, p = 0.033; Apolipoprotein C-III [APOCC3], ~2.63-fold change, p = 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain [GP1BA], ~9.18-fold change, p < 0.0001; Platelet basic protein [PPBP], ~4.72-fold change, p = 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was successfully validated in a separate cohort of 43 individual angina patients using Luminex analysis of the representative EV proteins C1QA (p = 0.005) and C5 (p = 0.0021), which act as critical regulators of complement activity in MI. We further present that all EV-derived fibrinogen components detected were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, and indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data urge the further development of novel EV-based diagnostic and therapeutic strategies to benefit patients with CAD.
HostingRepository	PRIDE
AnnounceDate	2016-05-31
AnnouncementXML	Submission_2016-05-31_03:33:22.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Esther Cheow
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ FT

Revision	Datetime	Status	ChangeLog Entry
0	2015-09-21 02:04:01	ID requested
⏵ 1	2016-05-31 03:33:24	announced

Cheow ES, Cheng WC, Lee CN, de Kleijn D, Sorokin V, Sze SK, Plasma-derived Extracellular Vesicles Contain Predictive Biomarkers and Potential Therapeutic Targets for Myocardial Ischemic (MI) Injury. Mol Cell Proteomics, 15(8):2628-40(2016) [pubmed]

submitter keyword: Cardiovascular disease

Exosomes

Label-free quantification

Plasma or serum analysis

Biomarker: Diagnostic

Extracellular vesicles

Newman Siu Kwan SZE
contact affiliation	Associate Professor Director of Proteomics and Mass Spectrometry Facility School of Biological Sciences Nanyang Technological University 60 Nanyang Drive, Singapore 637551 Tel: (65) 6514-1006; Fax: (65) 6791-3856 Email: sksze@ntu.edu.sg Web: http://proteomics.sbs.ntu.edu.sg/
contact email	sksze@ntu.edu.sg
lab head
Esther Cheow
contact affiliation	Nanyang Technological University
contact email	shcheow1@e.ntu.edu.sg
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/2016/05/PXD002950

PRIDE project URI

• PRIDE
  1. PXD002950
     1. Label: PRIDE project
     2. Name: Plasma-derived extracellular vesicles contain predictive biomarkers and potential therapeutic targets for myocardial ischemic injury