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ADAMTS-1 in abdominal aortic aneurysm
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden.
Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden.
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, e0178729Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Extracellular matrix degradation is a hallmark of abdominal aortic aneurysm (AAA). Among proteases that are capable of degrading extracellular matrix are a disintegrin and metalloproteases with thrombospondin motifs (ADAMTS). Pathogenesis of these proteases in AAA has not been investigated until date.

METHODS AND RESULTS: Human aneurysmal and control aortas were collected and analyzed with RT-PCR measuring the ADAMTS-1, 4,5,6,8,9,10,13,17 and ADAMTSL-1. Expression of a majority of the investigated ADAMTS members on mRNA level was decreased in aneurysm compared to control aorta. ADAMTS-1 was one of the members that was reduced most. Protein analysis using immunohistochemistry and western blot for localization and expression of ADAMTS-1 revealed that ADAMTS-1 was present predominantly in areas of SMCs and macrophages in aneurysmal aorta and higher expressed in AAA compared to control aortas. The role of ADAMTS-1 in AAA disease was further examined using ADAMTS-1 transgenic/apoE-/- mice with the experimental angiotensin II induced aneurysmal model. Transgenic mice overexpressing ADAMTS-1 showed to be similar to ADAMTS-1 wild type mice pertaining collagen, elastin content and aortic diameter.

CONCLUSION: Several of the ADAMTS members, and especially ADAMTS-1, are down regulated at mRNA level in AAA, due to unknown mechanisms, at the same time ADAMTS-1 protein is induced. The cleavage of its substrates, don't seem to be crucial for the pathogenesis of AAA but rather more important in the development of thoracic aortic aneurysm and atherosclerosis as shown in previous studies.

Place, publisher, year, edition, pages
Public Library of Science , 2017. Vol. 12, no 6, e0178729
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-139129DOI: 10.1371/journal.pone.0178729ISI: 000402611800112PubMedID: 28570682Scopus ID: 2-s2.0-85020220425OAI: oai:DiVA.org:liu-139129DiVA: diva2:1118883
Note

Funding agencies: Swedish Research Council [2016-02626]; Swedish Heart-Lung Foundation [20160779, 2013-0650]; Ake Wibergs stiftelse [M16-0070]

Available from: 2017-07-03 Created: 2017-07-03 Last updated: 2017-11-29Bibliographically approved

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Länne, Toste

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Vorkapic, EminaFolkesson, MaggieLänne, TosteWågsäter, Dick
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Division of Drug ResearchFaculty of Medicine and Health SciencesDepartment of Medical and Health SciencesDivision of Cardiovascular MedicineDepartment of Thoracic and Vascular Surgery
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