Dataset Information

ECM characterization of aortas from Adamts5+/+ and Adamts5∆cat AngII-treated mice by LC-MS/MS

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Aorta

DISEASE(S): Dilatation Of The Ascending Aorta

SUBMITTER: Xiaoke Yin

LAB HEAD: Manuel Mayr

PROVIDER: PXD009410 | Pride | 2018-05-08

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Marika_Mouse_ATS5_AngII_Top15_20161110_KO_19.raw	Raw
	Marika_Mouse_ATS5_AngII_Top15_20161110_KO_20.raw	Raw
	Marika_Mouse_ATS5_AngII_Top15_20161110_KO_21.raw	Raw
	Marika_Mouse_ATS5_AngII_Top15_20161110_KO_23.raw	Raw
	Marika_Mouse_ATS5_AngII_Top15_20161110_KO_24.raw	Raw

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Publications

Role of ADAMTS-5 in Aortic Dilatation and Extracellular Matrix Remodeling.

Fava Marika M Barallobre-Barreiro Javier J Mayr Ursula U Lu Ruifang R Didangelos Athanasios A Baig Ferheen F Lynch Marc M Catibog Norman N Joshi Abhishek A Barwari Temo T Yin Xiaoke X Jahangiri Marjan M Mayr Manuel M

Arteriosclerosis, thrombosis, and vascular biology 20180405 7

<h4>Objective</h4>Thoracic aortic aneurysm (TAA), a degenerative disease of the aortic wall, is accompanied by changes in the structure and composition of the aortic ECM (extracellular matrix). The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of proteases has recently been implicated in TAA formation. This study aimed to investigate the contribution of ADAMTS-5 to TAA development.<h4>Approach and results</h4>A model of aortic dilatation by AngII (angiotensin II) ...[more]

PMID: 29622560

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