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学科主题: 临床医学
题名:
20-Hydroxyeicosatetraenoic acid involved in endothelial activation and thrombosis
作者: Wang, Jiaxing1; Li, Hua2; He, Jinlong4; Li, Bochuan3,4; Bao, Qiankun3,4; Zhang, Xu3,4; Lv, Zhizhen5; Zhang, Youyi5; Han, Jingyan6; Ai, Ding3,4; Zhu, Yi1,3,4
关键词: von Willebrand factor ; 20-HETE ; endothelial cells
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
发表日期: 2015-06-01
DOI: 10.1152/ajpheart.00802.2014
卷: 308, 期:11, 页:H1359-H1367
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems ; Physiology ; Peripheral Vascular Disease
研究领域[WOS]: Cardiovascular System & Cardiology ; Physiology
关键词[WOS]: VON-WILLEBRAND-FACTOR ; KAPPA-B ACTIVATION ; ARTERIAL THROMBOSIS ; TISSUE FACTOR ; CELLS ; DYSFUNCTION ; DISEASE ; PATHWAY ; BLOOD ; HYPERTENSION
英文摘要:

Endothelial cells play an important role in the process of coagulation and the function of platelets. We have previously reported that 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite of arachidonic acid, increased platelet aggregation and induced hemostasis. The purpose of the present study is to investigate whether 20-HETE-mediated endothelial activation has effect on the coagulation and platelet aggregation. C57Bl/6 mice were treated with PBS or 20-HETE (20 mu g/kg) for 2 h, and then we performed a carotid artery or femoral artery thrombosis model by FeCl3. Detection of blood flow indicated that 20-HETE pretreatment accelerated formation of thrombus in both common carotid artery and femoral artery. In vitro, the secretion and expression of von Willebrand factor (vWF) in cultured human umbilical vein endothelial cells (HUVECs) with 20-HETE stimulation were increased, subsequently. The protein level of vWF in HUVECs was decreased at 1 h but increased with prolonged treatment with 20-HETE (> 4 h). In contrast, vWF in the culture medium was increased under administration of 20-HETE at 1 h. As a result, adhesion of platelets on HUVECs was significantly increased by 20-HETE. In HUVECs, the extracellular signal-regulated kinase (ERK) pathway was activated by 20-HETE in a dose-dependent manner, and the inhibitors of ERK and L-type Ca2+ channel blocked the release of vWF mediated by 20-HETE. In conclusion, 20-HETE instigates endothelial activation and induces the expression and secretion of vWF via the activation of ERK and calcium channel and therefore triggers thrombosis.

语种: 英语
所属项目编号: 2012CB517504 ; 81130002 ; 81100113 ; 81400320
项目资助者: Major National Basic Research Grant of China ; National Natural Science Foundation of China
WOS记录号: WOS:000356269600007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56622
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China
2.Dalian Med Univ, Dept Pharmacol, Coll Pharm, Dalian, Liaoning, Peoples R China
3.Tianjin Med Univ, Collaborat Innovat Ctr Tianjin Med Epigenet, Tianjin, Peoples R China
4.Tianjin Med Univ, Dept Physiol & Pathophysiol, Tianjin, Peoples R China
5.Peking Univ, Hosp 3, Inst Vasc Med, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing 100871, Peoples R China
6.Peking Univ, Hlth Sci Ctr, Tasly Microcirculat Res Ctr, Beijing 100871, Peoples R China

Recommended Citation:
Wang, Jiaxing,Li, Hua,He, Jinlong,et al. 20-Hydroxyeicosatetraenoic acid involved in endothelial activation and thrombosis[J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY,2015,308(11):H1359-H1367.
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