PXD020276

PXD020276 is an original dataset announced via ProteomeXchange.

Title	Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation: exploration of platelet proteome and lipidome.
Description	Hyperlipidemia is a well-established risk factor for cardiovascular diseases. Trillions of people worldwide display mildly elevated levels of plasma lipids and cholesterol due to diet and life-style. The relationship between severe hyperlipidemia and thrombosis has been extensively investigated, but the effects of the preliminary stages of hyperlipidemia on platelet function are unclear. Therefore, we investigated how moderate elevation of different plasma lipid profiles influence platelet activation and thrombus formation, as compared to higher plasma lipid concentrations. Hyperlipidemic Apoe-/- and Ldlr-/- and wild-type mice were fed a normal chow diet, resulting in mildly increased plasma cholesterol. Blood from both knockout mice was used in comparison to wild-type mice, for multiparameter ex vivo measurements of thrombus formation under flow. Whole blood (fibrin-)thrombus formation on collagen in the absence or presence of coagulation (with(out) tissue factor), indicated enhancement of the thrombotic process in both knockout mice. These effects were not further aggravated in aged mice, as well as in Apoe-/- mice on high fat diet with very high plasma cholesterol levels. Bone marrow chimeras of wild-type or Ldlr-/- platelets into irradiated Ldlr-/- recipient mice showed similar thrombus formation patterns. This suggested that hyperlipidemia itself, not the platelet LDL receptor deficiency is responsible for the altered platelet activation status in Ldlr-/- mice. Exploration of the platelet proteome revealed high similarity between the three genotypes, although some proteins showed significantly changed expression in Apoe-/- mice. Finally, platelet lipidomic analysis showed an increased lipid profile in mildly hyperlipidemic mice, which may further contribute to the observed prothrombotic phenotype
HostingRepository	PRIDE
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-04_12:55:58.198.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fiorella Andrea Solari
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-09 02:57:26	ID requested
⏵ 1	2021-03-04 12:55:59	announced

van Geffen JP, Swieringa F, van Kuijk K, Tullemans BME, Solari FA, Peng B, Clemetson KJ, Farndale RW, Dubois LJ, Sickmann A, Zahedi RP, Ahrends R, Biessen EAL, Sluimer JC, Heemskerk JWM, Kuijpers MJE, Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome. Sci Rep, 10(1):21407(2020) [pubmed]

submitter keyword: mouse platelets, coagulation, platelet activation, proteomics, thrombus formation, hyperlipidemia

Albert Sickmann
contact affiliation	Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
contact email	albert.sickmann@isas.de
lab head
Fiorella Andrea Solari
contact affiliation	Leibniz-Institut für Analytische Wissenschaften – ISAS – e.V.
contact email	fiorella.solari@isas.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020276
     1. Label: PRIDE project
     2. Name: Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation: exploration of platelet proteome and lipidome.