UM  > Institute of Chinese Medical Sciences
Inhibition of bone morphogenic protein 4 restores endothelial function in db/db diabetic mice
Zhang Y.1; Liu J.1; Tian X.Y.3; Wong W.T.3; Chen Y.1; Wang L.1; Luo J.1; Cheang W.S.1; Lau C.W.1; Kwan K.M.1; Wang N.2; Yao X.1; Huang Y.1
2014
Source PublicationArteriosclerosis, Thrombosis, and Vascular Biology
ISSN10795642 15244636
Volume34Issue:1Pages:152-159
Abstract

OBJECTIVE - Bone morphogenic protein 4 (BMP4) is involved in the development of endothelial dysfunction in hypertension. This study investigated whether the inhibition of BMP4 signaling improves endothelial function in db/db diabetic mice. APPROACH AND RESULTS - Male db/db mice were treated with noggin via osmotic pump infusion (1 μg/[h·kg]) for 2 weeks. Adenovirus BMP4-short hairpin RNA was introduced via tail vein injection at a dosage of 10 pfu/mouse and its effects were examined 7 days after. Vasoreactivity was studied on wire and pressure myograph. Both noggin treatment and adenovirus BMP4-short hairpin RNA transduction improved endothelium-dependent relaxations in aortae and flow-mediated dilatation in mesenteric arteries of db/db mice. Ex vivo treatment with BMP4 inhibitors and adenovirus BMP4-short hairpin RNA rescued the impaired endothelium-dependent relaxations in db/db mouse aortae and reduced reactive oxygen species overproduction determined by dihydroethidium staining, CM-H2DCFDA fluorescence imaging, and chemiluminescence assay in db/db mouse aortae, and also in ex vivo cultured C57BL/6 mouse aortae or primary mouse aortic endothelial cells treated with high glucose. Likewise, activin receptor-like kinase 3 silencing by short hairpin RNA lentivirus improved endothelium-dependent relaxations in db/db mouse aortae accompanied by reactive oxygen species inhibition in endothelial cells. In addition, noggin reduced BMP4 upregulation in high-glucose-treated endothelial cells and in C57BL/6 mouse aortae and in aortae from db/db mice. CONCLUSIONS - Inhibition of BMP4/activin receptor-like kinase 3/reactive oxygen species signaling improved endothelial function in diabetic mice through limiting oxidative stress in endothelium. Inhibiting BMP4 cascade can become another potential therapeutic strategy against diabetic vascular dysfunction. © 2013 American Heart Association, Inc.

KeywordBone Morphogenetic Protein 4, Mouse Diabetes Mellitus Endothelial Dysfunction Reactive Oxygen Species
DOI10.1161/ATVBAHA.113.302696
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaHematology ; Cardiovascular System & Cardiology
WOS SubjectHematology ; Peripheral Vascular Disease
WOS IDWOS:000337731100021
Fulltext Access
Citation statistics
Cited Times [WOS]:26   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Chinese University of Hong Kong
2.Peking University Health Science Center
3.Methodist Hospital Houston
Recommended Citation
GB/T 7714
Zhang Y.,Liu J.,Tian X.Y.,et al. Inhibition of bone morphogenic protein 4 restores endothelial function in db/db diabetic mice[J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2014,34(1):152-159.
APA Zhang Y.,Liu J.,Tian X.Y.,Wong W.T.,Chen Y.,Wang L.,Luo J.,Cheang W.S.,Lau C.W.,Kwan K.M.,Wang N.,Yao X.,&Huang Y..(2014).Inhibition of bone morphogenic protein 4 restores endothelial function in db/db diabetic mice.Arteriosclerosis, Thrombosis, and Vascular Biology,34(1),152-159.
MLA Zhang Y.,et al."Inhibition of bone morphogenic protein 4 restores endothelial function in db/db diabetic mice".Arteriosclerosis, Thrombosis, and Vascular Biology 34.1(2014):152-159.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Zhang Y.]'s Articles
[Liu J.]'s Articles
[Tian X.Y.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Zhang Y.]'s Articles
[Liu J.]'s Articles
[Tian X.Y.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhang Y.]'s Articles
[Liu J.]'s Articles
[Tian X.Y.]'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.