title: 20-Hydroxyeicosatetraenoic acid involved in endothelial activation and thrombosis.
abstract: 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 μg/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 Ca(2+) 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.
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China;
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China;
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China;
authors.forename: Jinlong
authors.initials: J
authors.lastname: He
authors.affiliation: Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China;
authors.forename: Bochuan
authors.initials: B
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China;
authors.forename: Qiankun
authors.initials: Q
authors.lastname: Bao
authors.affiliation: Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China;
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Vascular Medicine of Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Beijing, China; and.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Institute of Vascular Medicine of Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Beijing, China; and.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Han
authors.affiliation: Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China;
authors.forename: Ding
authors.initials: D
authors.lastname: Ai
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China; Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China; zhuyi@tijmu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D010974:Platelet Aggregation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000097:blood* / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D006893:Hydroxyeicosatetraenoic Acids; D047428:Protein Kinase Inhibitors; D014841:von Willebrand Factor; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid
keywords: 20-HETE; endothelial cells; von Willebrand factor