PXD020204-1

PXD020204 is an original dataset announced via ProteomeXchange.

Title	A phosphoproteomic analysis of platelets in severe obesity uncovers platelet reactivity and signaling pathways alterations
Description	Objective: Obesity is associated with a pro-inflammatory and pro-thrombotic state that supports atherosclerosis progression. The goal of this study was to gain insights into the phosphorylation events related to platelet reactivity in obesity and identify platelet biomarkers and altered activation pathways in this clinical condition. Approach and Results: We performed a comparative phosphoproteomic analysis of resting platelets from obese patients and their age- and gender-matched lean controls. The phosphoproteomic data were validated by mechanistic, functional and biochemical assays. We identified 220 differentially regulated phosphopeptides, from at least 175 proteins; interestingly all were up-regulated in obesity. Most of the altered phosphoproteins are involved in Src-family kinases (SFKs)-related signaling pathways, cytoskeleton reorganization and vesicle transport, some of them validated by targeted mass spectrometry. To confirm platelet dysfunction, flow cytometry assays were performed in whole blood indicating higher surface levels of glycoprotein (GP) VI and C-type lectin-like (CLEC) -2 in platelets from obese patients correlating positively with BMI. ROC curves analysis suggested a much higher sensitivity for GPVI to discriminate between obese and lean individuals. Indeed, we also found that obese platelets displayed more adhesion to collagen-coated plates. In line with the above data, sGPVI levels - indicative of higher GPVI signaling activation - were almost double in plasma from obese patients. Conclusion: Our results provide novel information on platelet phosphorylation changes related to obesity, revealing the impact of this chronic pathology on platelet reactivity and pointing towards the main signaling pathways dysregulated.
HostingRepository	PRIDE
AnnounceDate	2022-02-23
AnnouncementXML	Submission_2022-02-23_09:13:20.910.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Montserrat Carrascal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-05 23:38:57	ID requested
⏵ 1	2022-02-23 09:13:21	announced
2	2024-10-22 05:33:41	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: platelets, obesity, quantitative phosphoproteomics, biomarkers

Angel García Alonso
contact affiliation	1Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade Santiago de Compostela; and Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
contact email	angel.garcia@usc.e
lab head
Montserrat Carrascal
contact affiliation	IIBB-CSIC
contact email	montserrat.carrascal.csic@uab.cat
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/2022/02/PXD020204

PRIDE project URI

• PRIDE
  1. PXD020204
     1. Label: PRIDE project
     2. Name: A phosphoproteomic analysis of platelets in severe obesity uncovers platelet reactivity and signaling pathways alterations