PXD044594

PXD044594 is an original dataset announced via ProteomeXchange.

Title	Differential regulation of metabolome and proteome of plasma and CM EVs in HC
Description	Extracellular vesicles (EV) are cell-secreted, nano-sized membrane particles with various molecular cargo, including metabolites, proteins and nucleic acids [1] . EVs are involved in various physiological and pathological functions, including that of the myocardium [2] , such as cardiac stress adaptation mechanisms [3] . Metabolic co-morbidities can ameliorate the innate stress response of the heart [4], [5] . Furthermore, one of the most common metabolic co-morbidities, type-II diabetes, can inhibit EV- mediated cardioprotection [6] . EVs of high-fat fed animals can also exacerbate ischemic cardiac damage and induce cell death of cardiomyocytes (CM) [7], [8] . Therefore, metabolic diseases might interfere with the effect of cardiac EVs by various mechanisms. However, as of now, little is known about the effect of hypercholesterolemia (HC) on cardiovascular EV communication. Analyzing EVs of the circulation might lead to novel diagnostic tools and to better understanding of disease conditions. As of now it is evidenced that circulating EV number is increased in metabolic diseases [9]–[11] , including familiar hypercholesterolemia [12], [13] , in which their amount is associated with the risk of cardiovascular diseases [14], [15] as well. However, to understand the biological role of EV-related changes in cardiometabolic diseases, characterization of EV composition is needed. The main molecular constituents of EVs are membrane lipids and other metabolites, intravesicular and transmembrane proteins and nucleotides. Change in any of these constituents may result in an altered biological response. Barrachina et. al. has analyzed the dysregulated protein composition of circulating EVs in obesity [16] and in a similar study, miRNA cargo of EVs from obese patients was analyzed, as well [17] , however, it has not been assessed if HC alters EV metabolome, thus, function. EVs contribute to response to various stresses in the myocardium [18] , but as of now, we do not know HC influences EV release of CMs. One of the major effects of HC is cardiac- and systemic inflammation [19] . Earlier studies showed in various disease conditions, such as angiotensin II-induced hypertrophy, that CM EVs activate monocytes, thereby contribute to inflammation [20], [21] . In contrast, in hypoxic conditions, EVs promote macrophage polarization to the reparative M2 phenotype [22], [23] . Thus, we hypothesized that CM EVs might play a role in HC-induced cardiac inflammation. In this study, we aimed to analyze how HC affects the metabolic composition of EVs and how HC modifies CM EV communication. Therefore, we have analyzed the metabolome of circulating EVs of HC- fed rats and compared the identified changes to the plasma metabolome. In addition, for the first time, we assessed how HC affects the biophysical and biochemical properties of CM EVs and we analyzed their role in immune activation.
HostingRepository	PRIDE
AnnounceDate	2024-06-16
AnnouncementXML	Submission_2024-06-15_23:21:21.892.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kieran Wynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-15 09:14:08	ID requested
⏵ 1	2024-06-15 23:21:22	announced

10.1038/s41598-024-62689-6;

Kov, á, csh, á, zi C, Hambalk, ó S, Sayour NV, Gergely TG, Brenner GB, Pelyhe C, Kapui D, Weber BY, H, ü, ltenschmidt AL, P, á, llinger É, Buz, á, s EI, Zolcs, á, k Á, Kiss B, Boz, ó T, Cs, á, nyi C, K, ó, sa N, Kellermayer M, Farkas R, Karvaly GB, Wynne K, Matallanas D, Ferdinandy P, Giricz Z, Effect of hypercholesterolemia on circulating and cardiomyocyte-derived extracellular vesicles. Sci Rep, 14(1):12016(2024) [pubmed]

submitter keyword: TimsTOF Pro,Hypercholesterolemia, Metabolome, Proteome, EVs

Prof Zoltán Giricz
contact affiliation	1.Semmelweis University, Department of Pharmacology and Pharmacotherapy, Budapest, Hungary. 2.Pharmahungary Group, Szeged, Hungary
contact email	giricz.zoltan@med.semmelweis-univ.hu
lab head
Kieran Wynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
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/2024/06/PXD044594

PRIDE project URI

• PRIDE
  1. PXD044594
     1. Label: PRIDE project
     2. Name: Differential regulation of metabolome and proteome of plasma and CM EVs in HC