Format

Send to

Choose Destination
Am J Physiol Heart Circ Physiol. 2015 Jun 1;308(11):H1359-67. doi: 10.1152/ajpheart.00802.2014. Epub 2015 Mar 27.

20-Hydroxyeicosatetraenoic acid involved in endothelial activation and thrombosis.

Author information

1
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China;
2
Department of Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China;
3
Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China;
4
Institute of Vascular Medicine of Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Beijing, China; and.
5
Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
6
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.

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.

KEYWORDS:

20-HETE; endothelial cells; von Willebrand factor

PMID:
25820395
DOI:
10.1152/ajpheart.00802.2014
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center