PXD060700

PXD060700 is an original dataset announced via ProteomeXchange.

Title	Aorta proteomic analysis thoracic-abdominal
Description	Aortic aneurysms is increasing as the human population ages. Pathological oxidative stress is implicated in development of aortic aneurysms. We pursued a chemogenetic approach to create an animal model of aortic aneurysm formation using a transgenic mouse line DAAO-TGTie2 that expresses yeast D-amino acid oxidase (DAAO) under control of the endothelial Tie2 promoter. In DAAO-TGTie2 mice, DAAO generates the reactive oxygen species hydrogen peroxide (H2O2) in endothelial cells only when provided with D-amino acids. When DAAO-TGTie2 mice are chronically fed D-alanine, the animals become hypertensive and develop abdominal but not thoracic aortic aneurysms. Generation of H2O2 in the endothelium leads to oxidative stress throughout the vascular wall. Proteomic analyses indicate that the oxidant-modulated protein kinase JNK1 is dephosphorylated by the phophoprotein phosphatase DUSP3 in abdominal but not thoracic aorta, causing activation of KLF4-dependent transcriptional pathways that trigger phenotypic switching and aneurysm formation. Pharmacological DUSP3 inhibition completely blocks aneurysm formation caused by chemogenetic oxidative stress. These studies establish that regional differences in oxidant-modulated signaling pathways lead to differential disease progression in discrete vascular beds, and identify DUSP3 as a potential pharmacological target for the treatment of aortic aneurysms.
HostingRepository	PRIDE
AnnounceDate	2025-02-18
AnnouncementXML	Submission_2025-02-18_08:09:16.292.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Michel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-11 14:50:16	ID requested
⏵ 1	2025-02-18 08:09:16	announced

Dataset with its publication pending

submitter keyword: Oxidative stress, Vascular Biology, Chemogenetics, Aneurysm

Prof.Thomas Michel
contact affiliation	Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
contact email	michel@hms.harvard.edu
lab head
Thomas Michel
contact affiliation	Professor, Brigham and Women's Hospital, Harvard Medical School
contact email	thomas_michel@hms.harvard.edu
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/2025/02/PXD060700

PRIDE project URI

• PRIDE
  1. PXD060700
     1. Label: PRIDE project
     2. Name: Aorta proteomic analysis thoracic-abdominal