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学科主题: 基础医学
题名:
Inhibition of Bone Morphogenic Protein 4 Restores Endothelial Function in db/db Diabetic Mice
作者: Zhang, Yang1; Liu, Jian2; Tian, Xiao Yu4; Wong, Wing Tak4; Chen, Yangchao2; Wang, Li1; Luo, Jiangyun1; Cheang, Wai San1; Lau, Chi Wai1; Kwan, Kin Ming3; Wang, Nanping5; Yao, Xiaoqiang1,2; Huang, Yu1,2
关键词: bone morphogenetic protein 4, mouse ; diabetes mellitus ; endothelial dysfunction ; reactive oxygen species
刊名: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
发表日期: 2014
DOI: 10.1161/ATVBAHA.113.302696
卷: 34, 期:1, 页:152-+
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Hematology ; Cardiovascular System & Cardiology
关键词[WOS]: PULMONARY-HYPERTENSION ; VASCULAR CALCIFICATION ; NADPH OXIDASES ; CELLS ; ATHEROSCLEROSIS ; EXPRESSION ; RECEPTOR ; ACTIVATION ; SIGNALS ; NOGGIN
英文摘要:

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 mu g/[h.kg(-1)]) for 2 weeks. Adenovirus BMP4-short hairpin RNA was introduced via tail vein injection at a dosage of 10(9) 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-H(2)DCFDA 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.

语种: 英语
所属项目编号: CUHK2/CRF/12G ; 466110 ; 2012CB517805
项目资助者: Hong Kong Collaborative Research Fund ; General Research Fund grants ; National Basic Research Program of China ; Chinese University of Hong Kong Focused Investment Scheme B
WOS记录号: WOS:000337731100021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59506
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Inst Vasc Med, Hong Kong, Hong Kong, Peoples R China
2.Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China
4.Houston Methodist Res Inst, Dept Cardiovasc Sci, Houston, TX USA
5.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100871, Peoples R China

Recommended Citation:
Zhang, Yang,Liu, Jian,Tian, Xiao Yu,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-+.
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