SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Role of ADAMTS (A Disintegrin and Metalloproteinase With Thrombospondin Motifs)-5 in Aortic Dilatation and Extracellular Matrix Remodeling.

Fava, M; Barallobre-Barreiro, J; Mayr, U; Lu, R; Didangelos, A; Baig, F; Lynch, M; Catibog, N; Joshi, A; Barwari, T; et al. 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 (2018) Role of ADAMTS (A Disintegrin and Metalloproteinase With Thrombospondin Motifs)-5 in Aortic Dilatation and Extracellular Matrix Remodeling. Arterioscler Thromb Vasc Biol, 38 (7). pp. 1537-1548. ISSN 1524-4636 https://doi.org/10.1161/ATVBAHA.117.310562
SGUL Authors: Jahangiri, Marjan

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (3MB) | Preview

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 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. APPROACH AND RESULTS: A model of aortic dilatation by AngII (angiotensin II) infusion was adopted in mice lacking the catalytic domain of ADAMTS-5 (Adamts5Δcat). Adamts5Δcat mice showed an attenuated rise in blood pressure while displaying increased dilatation of the ascending aorta (AsAo). Interestingly, a comparison of the aortic ECM from AngII-treated wild-type and Adamts5Δcat mice revealed versican as the most upregulated ECM protein in Adamts5Δcat mice. This was accompanied by a marked reduction of ADAMTS-specific versican cleavage products (versikine) and a decrease of LRP1 (low-density lipoprotein-related protein 1). 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.

Item Type: Article
Additional Information: © 2018 The Authors. Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
Keywords: aneurysm, blood pressure, extracellular matrix, mice, thrombospondin, aneurysm, blood pressure, extracellular matrix, mice, thrombospondin, Cardiovascular System & Hematology, 1103 Clinical Sciences, 1102 Cardiovascular Medicine And Haematology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Arterioscler Thromb Vasc Biol
ISSN: 1524-4636
Language: eng
Dates:
DateEvent
July 2018Published
5 April 2018Published Online
19 March 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
CH/16/3/32406British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
RG/16/14/32397British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PG/17/48/32956British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
PubMed ID: 29622560
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109733
Publisher's version: https://doi.org/10.1161/ATVBAHA.117.310562

Actions (login required)

Edit Item Edit Item