PXD009410

PXD009410 is an original dataset announced via ProteomeXchange.

Title	ECM characterization of aortas from Adamts5+/+ and Adamts5∆cat AngII-treated mice by LC-MS/MS
Description	Objective - Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic extracellular matrix (ECM). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development. Approach and Results - A model of aortic dilatation by angiotensin II (AngII) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat). Adamts5Δcat mice showed an attenuated rise in blood pressure whilst displaying increased dilatation of the ascending aorta. Interestingly, a comparison of the aortic ECM from AngII-treated wildtype and Adamts5Δcat mice revealed versican as the most up-regulated ECM protein in Adamts5Δcat mice. This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of low-density lipoprotein-related protein 1 (LRP1). Silencing LRP1 expression in human aortic smooth muscle cells reduced the expression of ADAMTS5, attenuated the generation of versikine but increased soluble ADAMTS-1. A similar increase in ADAMTS-1 was observed in aortas of AngII-treated Adamts5Δcat mice, but was not sufficient to maintain versican processing and prevent aortic dilatation. Conclusions - Our results support the emerging role of ADAMTS proteases in TAA. ADAMTS-5 rather than ADAMTS-1 is the key protease for versican regulation in murine aortas. Further studies are needed to define the ECM substrates of the different ADAMTS proteases and their contribution to TAA formation.
HostingRepository	PRIDE
AnnounceDate	2018-05-08
AnnouncementXML	Submission_2018-05-08_07:24:41.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD009410
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Xiaoke Yin
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation; Carbamidomethyl; Deamidated:18O(1)
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2018-04-05 01:27:01	ID requested
⏵ 1	2018-05-08 07:24:42	announced

Fava M, Barallobre-Barreiro J, Mayr U, Lu R, Didangelos A, Baig F, Lynch M, Catibog N, Joshi A, Barwari T, Yin X, Jahangiri M, Mayr M, Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling. Arterioscler Thromb Vasc Biol, 38(7):1537-1548(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: aneurysm, ascending aorta, extracellular matrix, protease, LC-MS/MS, Adamts

Manuel Mayr
contact affiliation	King's British Heart Foundation Centre, King's College London, London, UK
contact email	manuel.mayr@kcl.ac.uk
lab head
Xiaoke Yin
contact affiliation	Cardiovascular Division, King's College London
contact email	xiaoke.yin@kcl.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009410
     1. Label: PRIDE project
     2. Name: ECM characterization of aortas from Adamts5+/+ and Adamts5∆cat AngII-treated mice by LC-MS/MS