PXD023960

PXD023960 is an original dataset announced via ProteomeXchange.

Title	The amino acid homoarginine inhibits atherogenesis by modulating T-cell function
Description	Rational: Amino acid metabolism is crucial for inflammatory processes during atherogenesis. The endogenous amino acid homoarginine (HA) is a robust biomarker for cardiovascular outcome and mortality with high levels being protective. However, the underlying molecular mechanism remains elusive. Objective: We investigated the effect of HA supplementation on atherosclerotic plaque development with a particular focus on athero-inflammation. Methods and Results: Female apolipoprotein (Apo) E-deficient mice were supplemented with HA (14 mg/L) in drinking water starting two weeks before and continuing throughout a six week-course of Western-type diet (HA-treated). Control mice (Ctrl) received normal drinking water. HA supplementation led to a 2-fold increase in circulating HA concentrations. Plaque- and immunological phenotyping revealed that HA-treated mice exhibited a reduction in atherosclerosis in the aortic root as well as in the brachiocephalic trunk. A substantial decrease in lesion CD3+ T cells suggested a T cell-related effect of HA supplementation. Using mass spectrometry-based proteomics and subsequent pathway analysis together with conventional in vitro techniques such as flow cytometry, various migration and chemotaxis assays as well as super-resolution microscopy, we demonstrate that HA profoundly modulated the spatial organization of the T-cell actin cytoskeleton. Further mechanistic studies revealed an inhibition of T-cell activation and proliferation as well as a striking impairment of the migratory capacities of T cells in response to relevant chemokines by HA, all of which likely contribute to its atheroprotective effects. Conclusion: This study unravels a novel mechanism, by which the amino acid HA reduces atherosclerosis, namely the regulation of T-cell functions crucial for adaptive immunity. We identified that HA modulates the T-cell cytoskeleton and thereby mitigated important T-cell functions during atherogenesis. These findings provide a molecular explanation for the beneficial effects of HA in atherosclerotic cardiovascular disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:55:32.971.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ignasi Forne
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-03 01:56:04	ID requested
1	2023-01-30 01:57:08	announced
⏵ 2	2023-11-14 07:55:36	announced	2023-11-14: Updated project metadata.

Nitz K, Lacy M, Bianchini M, Wichapong K, K, ü, c, ü, kg, ö, ze IA, Bonfiglio CA, Migheli R, Wu Y, Burger C, Li Y, Forn, é I, Ammar C, Janjic A, Mohanta S, Duchene J, Heemskerk JWM, Megens RTA, Schwedhelm E, Huveneers S, Lygate CA, Santovito D, Zimmer R, Imhof A, Weber C, Lutgens E, Atzler D, The Amino Acid Homoarginine Inhibits Atherogenesis by Modulating T-Cell Function. Circ Res, 131(8):701-712(2022) [pubmed]

submitter keyword: homoarginine, actin cytoskeleton,Atherosclerosis, T cells, amino acids

Dorothee Atzler, PhD
contact affiliation	Institute for Cardiovascular Prevention (IPEK) Klinikum der Universität München, Ludwig-Maximilians-Universität München (LMU Munich) Pettenkoferstr. 9, D-80336 Munich, Germany Telefon: +49 (0)89 4400 - 54672
contact email	dorothee.atzler@med.uni-muenchen.de
lab head
Ignasi Forne
contact affiliation	Biomedical Center-LMU
contact email	ignasi.forne@lrz.uni-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023960
     1. Label: PRIDE project
     2. Name: The amino acid homoarginine inhibits atherogenesis by modulating T-cell function