PXD022829

PXD022829 is an original dataset announced via ProteomeXchange.

Title	Diminazene aceturate (DIZE) stabilizes atherosclerotic plaques and attenuates hepatic steatosis in apolipoprotein E knockout mice by influencing macrophages polarization and taurine biosynthesis
Description	Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are leading causes of morbidity and mortality in the Western countries. NAFLD is an important independent risk factor for the development of atherosclerosis. The renin-angiotensin system (RAS) with its two main opposing effectors: angiotensin II (Ang II) and Ang-(1-7) is widely recognized as a major regulator of cardiovascular function and body metabolic processes. Angiotensin-converting enzyme 2 (ACE2) by breaking-down Ang II forms Ang-(1-7) and thus favors Ang-(1-7) actions. Therefore, the aim of our study was to comprehensively evaluate the influence of prolonged treatment with ACE2 activator – diminazene aceturate (DIZE) on the development of atherosclerotic lesions and hepatic steatosis in apoE-/- mice fed a high-fat diet (HFD). We have shown that DIZE at a dose of 30 mg/kg/day given orally for 16 weeks was able to stabilize atherosclerotic lesions and attenuate hepatic steatosis in apoE-/- mice fed an HFD. Such effects were associated with decreased total macrophages content and increased α-smooth muscle actin levels in atherosclerotic plaques. Moreover, DIZE changed polarization of macrophages towards increased amount of anti-inflammatory M2 macrophages in atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated HDL in the plasma, decreased triglycerides levels and increased biosynthesis and concentration of taurine in liver of apoE-/- mice. However, the exact molecular mechanisms of both the anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_14:29:10.264.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aneta Stachowicz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iTRAQ8plex-116 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-01 01:20:26	ID requested
⏵ 1	2021-09-09 14:29:11	announced

Stachowicz A, Wi, ś, niewska A, Ku, ś K, Bia, ł, as M, Ł, omnicka M, Toto, ń, -, Ż, ura, ń, ska J, Kiepura A, Stachyra K, Suski M, Bujak-Gi, ż, ycka B, Jawie, ń J, Olszanecki R, Diminazene Aceturate Stabilizes Atherosclerotic Plaque and Attenuates Hepatic Steatosis in apoE-Knockout Mice by Influencing Macrophages Polarization and Taurine Biosynthesis. Int J Mol Sci, 22(11):(2021) [pubmed]

submitter keyword: atherosclerosis, fatty liver, DIZE, macrophages polarization, apoE-knockout mice, ACE2

Rafał Olszanecki
contact affiliation	Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland
contact email	rafal.olszanecki@uj.edu.pl
lab head
Aneta Stachowicz
contact affiliation	Department of Pharmacology, Jagiellonian University Medical College
contact email	aneta.stachowicz@uj.edu.pl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022829
     1. Label: PRIDE project
     2. Name: Diminazene aceturate (DIZE) stabilizes atherosclerotic plaques and attenuates hepatic steatosis in apolipoprotein E knockout mice by influencing macrophages polarization and taurine biosynthesis