IR@PKUHSC  > 北京大学第二临床医学院
学科主题临床医学
Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways
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
2013-06-01
DOI10.1038/cr.2013.56
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
资助者National Basic Research Program of China ; National Natural Science Foundation of China ; Priority Academic Program Development of Jiangsu Higher Education Institutions ; National Basic Research Program of China ; National Natural Science Foundation of China ; Priority Academic Program Development of Jiangsu Higher Education Institutions
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
资助者National Basic Research Program of China ; National Natural Science Foundation of China ; Priority Academic Program Development of Jiangsu Higher Education Institutions ; 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
引用统计
被引频次:10[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/400002259/57797
专题北京大学第二临床医学院
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
推荐引用方式
GB/T 7714
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.
APA Xiong, Yan.,Hu, Zhenqian.,Han, Xiaofan.,Jiang, Beibei.,Zhang, Rongli.,...&Luo, Jincai.(2013).Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways.CELL RESEARCH,23(6),820-834.
MLA Xiong, Yan,et al."Hypertensive stretch regulates endothelial exocytosis of Weibel-Palade bodies through VEGF receptor 2 signaling pathways".CELL RESEARCH 23.6(2013):820-834.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Xiong, Yan]的文章
[Hu, Zhenqian]的文章
[Han, Xiaofan]的文章
百度学术
百度学术中相似的文章
[Xiong, Yan]的文章
[Hu, Zhenqian]的文章
[Han, Xiaofan]的文章
必应学术
必应学术中相似的文章
[Xiong, Yan]的文章
[Hu, Zhenqian]的文章
[Han, Xiaofan]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。