IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
Inhibition of Bone Morphogenic Protein 4 Restores Endothelial Function in db/db Diabetic Mice
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
2014
DOI10.1161/ATVBAHA.113.302696
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
WOS记录号WOS:000337731100021
项目编号CUHK2/CRF/12G ; 466110 ; 2012CB517805
资助机构Hong Kong Collaborative Research Fund ; General Research Fund grants ; National Basic Research Program of China ; Chinese University of Hong Kong Focused Investment Scheme B
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59506
专题北京大学基础医学院_心血管所
北京大学基础医学院
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
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GB/T 7714
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-+.
APA Zhang, Yang.,Liu, Jian.,Tian, Xiao Yu.,Wong, Wing Tak.,Chen, Yangchao.,...&Huang, Yu.(2014).Inhibition of Bone Morphogenic Protein 4 Restores Endothelial Function in db/db Diabetic Mice.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,34(1),152-+.
MLA Zhang, Yang,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-+.
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