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学科主题: 临床医学
题名:
Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways
作者: Xiong, Yan1; Hu, Zhenqian1; Han, Xiaofan1; Jiang, Beibei1; Zhang, Rongli2; Zhang, Xiaoyu1; Lu, Yao1; Geng, Chenyang1; Li, Wei3; He, Yulong4; Huo, Yingqing1; Shibuya, Masabumi5; Luo, Jincai1
关键词: endothelial cells ; stretch ; VEGF receptor ; exocytosis of Weibel-Palade bodies
刊名: CELL RESEARCH
发表日期: 2013-06-01
DOI: 10.1038/cr.2013.56
卷: 23, 期:6, 页:820-834
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: WILLEBRAND-FACTOR RELEASE ; FLUID SHEAR-STRESS ; NITRIC-OXIDE SYNTHASE ; GROWTH-FACTOR VEGF ; VON-WILLEBRAND ; VASCULAR ENDOTHELIUM ; VONWILLEBRAND-FACTOR ; PORTAL-HYPERTENSION ; BODY EXOCYTOSIS ; CELLS
英文摘要:

Regulated endothelial exocytosis of Weibel-Palade bodies (WPBs), the first stage in leukocyte trafficking, plays a pivotal role in inflammation and injury. Acute mechanical stretch has been closely associated with vascular inflammation, although the precise mechanism is unknown. Here, we show that hypertensive stretch regulates the exocytosis of WPBs of endothelial cells (ECs) through VEGF receptor 2 (VEGFR2) signaling pathways. Stretch triggers a rapid release (within minutes) of von Willebrand factor and interleukin-8 from WPBs in cultured human ECs, promoting the interaction between leukocytes and ECs through the translocation of P-selectin to the cell membrane. We further show that hypertensive stretch significantly induces P-selectin translocation of intact ECs and enhances leukocyte adhesion both ex vivo and in vivo. Stretch-induced endothelial exocytosis is mediated via a VEGFR2/PLC gamma 1/calcium pathway. Interestingly, stretch also induces a negative feedback via a VEGFR2/Akt/nitric oxide pathway. Such dual effects are confirmed using pharmacological and genetic approaches in carotid artery segments, as well as in acute hypertensive mouse models. These studies reveal mechanical stretch as a potent agonist for endothelial exocytosis, which is modulated by VEGFR2 signaling. Thus, VEGFR2 signaling pathways may represent novel therapeutic targets in limiting hypertensive stretch-related inflammation.

语种: 英语
所属项目编号: 2012CB945100 ; 81170098 ; 81070115
项目资助者: National Basic Research Program of China ; National Natural Science Foundation of China ; Priority Academic Program Development of Jiangsu Higher Education Institutions
WOS记录号: WOS:000319807100012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57797
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China
2.Jobu Univ, Inst Physiol & Med, Takasaki, Gumma, Japan
3.Peking Univ, Inst Mol Med, Lab Vasc Biol, Beijing 100871, Peoples R China
4.Peking Univ, Inst Mol Med, Nonhuman Primate Res Ctr, Beijing 100871, Peoples R China
5.Soochow Univ, Cyrus Tang Hematol Ctr, Lab Vasc & Canc Biol, Suzhou 215325, Jiangsu, Peoples R China

Recommended Citation:
Xiong, Yan,Hu, Zhenqian,Han, Xiaofan,et al. Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways[J]. CELL RESEARCH,2013,23(6):820-834.
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