UM  > 健康科學學院
Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II
Takayanagi T.2; Forrester S.J.2; Kawai T.2; Obama T.2; Tsuji T.2; Elliott K.J.2; Nuti E.3; Rossello A.2; Kwok H.F.1; Scalia R.2; Rizzo V.2; Eguchi S.2
2016-10-01
Source PublicationHypertension
ISSN15244563 0194911X
Volume68Issue:4Pages:949-955
Abstract

Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications.

KeywordEnd-organ Damage Fibrosis Hypertension Renin Angiotensin System Signal Transduction
DOI10.1161/HYPERTENSIONAHA.116.07620
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCardiovascular System & Cardiology
WOS SubjectPeripheral Vascular Disease
WOS IDWOS:000384127800022
Fulltext Access
Citation statistics
Cited Times [WOS]:22   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Universidade de Macau
2.Temple University
3.Università di Pisa
Recommended Citation
GB/T 7714
Takayanagi T.,Forrester S.J.,Kawai T.,et al. Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II[J]. Hypertension,2016,68(4):949-955.
APA Takayanagi T..,Forrester S.J..,Kawai T..,Obama T..,Tsuji T..,...&Eguchi S..(2016).Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.Hypertension,68(4),949-955.
MLA Takayanagi T.,et al."Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II".Hypertension 68.4(2016):949-955.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Takayanagi T.]'s Articles
[Forrester S.J.]'s Articles
[Kawai T.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Takayanagi T.]'s Articles
[Forrester S.J.]'s Articles
[Kawai T.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Takayanagi T.]'s Articles
[Forrester S.J.]'s Articles
[Kawai T.]'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.