UM  > 健康科學學院
Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile-Induced Abdominal Aortic Aneurysm
Kawai T.2; Takayanagi T.2; Forrester S.J.2; Preston K.J.2; Obama T.2; Tsuji T.2; Kobayashi T.2; Boyer M.J.2; Cooper H.A.2; Kwok H.F.1; Hashimoto T.3; Scalia R.2; Rizzo V.2; Eguchi S.2
2017-11-01
Source PublicationHypertension
ISSN15244563 0194911X
Volume70Issue:5Pages:959-963
Abstract

Angiotensin II (AngII)-activated epidermal growth factor receptor has been implicated in abdominal aortic aneurysm (AAA) development. In vascular smooth muscle cells (VSMCs), AngII activates epidermal growth factor receptor via a metalloproteinase, ADAM17 (a disintegrin and metalloproteinase domain 17). We hypothesized that AngII-dependent AAA development would be prevented in mice lacking ADAM17 in VSMCs. To test this concept, control and VSMC ADAM17-deficient mice were cotreated with AngII and a lysyl oxidase inhibitor, β-aminopropionitrile, to induce AAA. We found that 52.4% of control mice did not survive because of aortic rupture. All other surviving control mice developed AAA and demonstrated enhanced expression of ADAM17 in the AAA lesions. In contrast, all AngII and β-aminopropionitrile-treated VSMC ADAM17-deficient mice survived and showed reduction in external/internal diameters (51%/28%, respectively). VSMC ADAM17 deficiency was associated with lack of epidermal growth factor receptor activation, interleukin-6 induction, endoplasmic reticulum/oxidative stress, and matrix deposition in the abdominal aorta of treated mice. However, both VSMC ADAM17-deficient and control mice treated with AngII and β-aminopropionitrile developed comparable levels of hypertension. Treatment of C57Bl/6 mice with an ADAM17 inhibitory antibody but not with control IgG also prevented AAA development. In conclusion, VSMC ADAM17 silencing or systemic ADAM17 inhibition seems to protect mice from AAA formation. The mechanism seems to involve suppression of epidermal growth factor receptor activation.

KeywordAneurysm Angiotensin Ii Hypertension Rupture Signal Transduction
DOI10.1161/HYPERTENSIONAHA.117.09822
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCardiovascular System & Cardiology
WOS SubjectPeripheral Vascular Disease
WOS IDWOS:000413010300018
PublisherLIPPINCOTT WILLIAMS & WILKINS
Fulltext Access
Citation statistics
Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Universidade de Macau
2.Temple University
3.University of California, San Francisco
Recommended Citation
GB/T 7714
Kawai T.,Takayanagi T.,Forrester S.J.,et al. Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile-Induced Abdominal Aortic Aneurysm[J]. Hypertension,2017,70(5):959-963.
APA Kawai T..,Takayanagi T..,Forrester S.J..,Preston K.J..,Obama T..,...&Eguchi S..(2017).Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile-Induced Abdominal Aortic Aneurysm.Hypertension,70(5),959-963.
MLA Kawai T.,et al."Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/β-Aminopropionitrile-Induced Abdominal Aortic Aneurysm".Hypertension 70.5(2017):959-963.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Kawai T.]'s Articles
[Takayanagi T.]'s Articles
[Forrester S.J.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Kawai T.]'s Articles
[Takayanagi T.]'s Articles
[Forrester S.J.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Kawai T.]'s Articles
[Takayanagi T.]'s Articles
[Forrester S.J.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.