PXD029562

PXD029562 is an original dataset announced via ProteomeXchange.

Title	Accelerated age-dependent development of endothelial dysfunction in humanized dyslipidemic mice
Description	In the present work endothelial function in the aorta and femoral artery assessed in vivo by magnetic resonance imaging (MRI) was characterized in male and female 8-, 14-, 22-, 28-, and 40-week-old E3L.CETP and C57BL/6J mice. Vascular nitric oxide (NO), eicosanoids and hydrogen peroxide (H2O2) production in the aorta, were measured by electron paramagnetic resonance spectroscopy (EPR), mass spectrometry (LC/MS) and fluoresence assay, respectively. Endothelial-specific protein plasma biomarkers and global alterations in plasma proteome were asssesed by targeted and non-targeted preotomics, respectively. In C57BL/6J endothelial dysfunction was observed in 40-week-old female and male mice as evidenced by impaired endothelium-dependent vasodilation induced by acetylcholine (Ach) in the aorta or by flow in the femoral artery (flow-mediated vasodilation, FMD). In E3L.CETP mice age-dependent endothelial dysfunction was accelerated and appeared in 14-22-week-old male and 22-28-week-old female mice. In 40 week-old E3L.CETP mice endothelial dysfunction was severe in both male and female mice and was more pronounced as compared with age-matched C57BL/6J mice. Despite severe endothelial dysfunction in 40 week-old mice E3L.CETP mice neither in the aortic roots nor in brachiocephalic artery atherosclerotic plaques were not detected. Interestingly, in the presence of NOS-inhibitor (L-NAME), FMD was inhibited in all experimental groups. However, effect of L-NAME on Ach–induced vasodilation in E3L.CETP mice, was blunted as compared with C57BL/6J mice, in particular in young E3L.CETP female mice. Furthermore, Ach–induced vasodilation in the aorta was inhibited by catalase, while H2O2 production was increased, in young female but not in male E3L.CETP mice. A switch from NO to H2O2-dependent vasodilation in young female E3L.CETP mice was associated with a blunted systemic inflammation and lower number of differentially expressed proteins (DEPs) in plasma than in young E3L.CETP male mice as compared with age-and sex-matched C57BL/6J mice. However, female and male 40-week-old E3L.CETP mice displayed similar number of DEPs in plasma vs respective sex-matched younger E3L.CETP mice. In the present work endothelial function in the aorta and femoral artery assessed in vivo by magnetic resonance imaging (MRI) was characterized in male and female 8-, 14-, 22-, 28-, and 40-week-old E3L.CETP and C57BL/6J mice. Vascular nitric oxide (NO), eicosanoids and hydrogen peroxide (H2O2) production in the aorta, were measured by electron paramagnetic resonance spectroscopy (EPR), mass spectrometry (LC/MS) and fluoresence assay, respectively. Endothelial-specific protein plasma biomarkers and global alterations in plasma proteome were asssesed by targeted and non-targeted preotomics, respectively. In C57BL/6J endothelial dysfunction was observed in 40-week-old female and male mice as evidenced by impaired endothelium-dependent vasodilation induced by acetylcholine (Ach) in the aorta or by flow in the femoral artery (flow-mediated vasodilation, FMD). In E3L.CETP mice age-dependent endothelial dysfunction was accelerated and appeared in 14-22-week-old male and 22-28-week-old female mice. In 40 week-old E3L.CETP mice endothelial dysfunction was severe in both male and female mice and was more pronounced as compared with age-matched C57BL/6J mice. Despite severe endothelial dysfunction in 40 week-old mice E3L.CETP mice neither in the aortic roots nor in brachiocephalic artery atherosclerotic plaques were not detected. Interestingly, in the presence of NOS-inhibitor (L-NAME), FMD was inhibited in all experimental groups. However, effect of L-NAME on Ach–induced vasodilation in E3L.CETP mice, was blunted as compared with C57BL/6J mice, in particular in young E3L.CETP female mice. Furthermore, Ach–induced vasodilation in the aorta was inhibited by catalase, while H2O2 production was increased, in young female but not in male E3L.CETP mice. A switch from NO to H2O2-dependent vasodilation in young female E3L.CETP mice was associated with a blunted systemic inflammation and lower number of differentially expressed proteins (DEPs) in plasma than in young E3L.CETP male mice as compared with age-and sex-matched C57BL/6J mice. However, female and male 40-week-old E3L.CETP mice displayed similar number of DEPs in plasma vs respective sex-matched younger E3L.CETP mice.
HostingRepository	PRIDE
AnnounceDate	2025-06-30
AnnouncementXML	Submission_2025-06-29_16:43:07.616.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jacek Wisniewski
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	2021-11-04 10:16:43	ID requested
⏵ 1	2025-06-29 16:43:08	announced

Bar A, Berkowicz P, Kurpinska A, Mohaissen T, Kara, ś A, Kaczara P, Suraj-Pra, ż, mowska J, Sternak M, Marczyk B, Malinowska A, Kij A, Jasztal A, Czyzynska-Cichon I, Pieterman EJ, Princen HMG, Wi, ś, niewski JR, Chlopicki S, Effects of life-long hyperlipidaemia on age-dependent development of endothelial dysfunction in humanised dyslipidaemic mice. Geroscience, 47(3):2673-2701(2025) [pubmed]

10.1007/s11357-025-01578-w;

submitter keyword: qunatitative proteomics, humanized dyslipidemic mice, FASP,endothelial dysfunction, total protein approach

Jacek-Roman Wisniewski
contact affiliation	Max-Planck-Institute of Biochemistry, Martinsried, Germany
contact email	jwisniew@biochem.mpg.de
lab head
Jacek Wisniewski
contact affiliation	Proteomics
contact email	jwisniew@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029562
     1. Label: PRIDE project
     2. Name: Accelerated age-dependent development of endothelial dysfunction in humanized dyslipidemic mice