近日，泸州医学院药物与功能与食品研究中心吴剑波教授课题组，以任美萍为第一作者，吴剑波教授为通讯作者，在美国生理学杂志《American Journal of Physiology》上发表了题为“Endothelial cells but not platelets are the major source of Toll-like receptor 4 in the arterial thrombosis and tissue factor expression in mice”的研究论文。该论文由国家自然科学基金和四川省高校科技创新团队等课题资助，由泸州医学院药物与功能与食品研究中心为第一完成单位。

Am J Physiol Regul Integr Comp Physiol. 2014 Oct 1;307(7):R901-7. doi: 10.1152/ajpregu.00324.2014. Epub 2014 Aug 20.

Endothelial cells but not platelets are the major source of Toll-like receptor 4 in the arterial thrombosis and tissue factor expression in mice.

Ren M1, Li R1, Luo M1, Chen N1, Deng X1, Yan K1, Zeng M1, Wu J2.

Author information

1Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.2Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and Department of Internal Medicine, University of Missouri School of Medicine, Columbia, Missouri wuji@missouri.edu.

Abstract

It is known that Toll-like receptor (TLR)-4 plays an important role in myocardial infarction and atherothrombosis. The role of TLR-4 in arterial thrombosis is undefined. Both TLR-4-deficient (TLR-4(-/-)) and wild-type (WT) mice were subjected to FeCl3 carotid artery injury, and the time required to form an occlusive thrombus was measured. The mean time to occlusion in TLR-4(-/-) mice was significantly greater than that in WT mice after injury (303 ± 32 vs. 165 ± 34 s, P < 0.05). Furthermore, when we used a WT or TLR-4(-/-)-derived platelet reinfusion in a platelet depletion/reinfusion procedure, there was no significant change in the occlusion time and tissue factor (TF) activity in injured arteries between WT mice and platelet-depleted WT mice. Similarly, no significant difference was observed between TLR-4(-/-) mice and platelet-depleted TLR-4(-/-) mice for the WT or TLR-4(-/-)-derived platelet reinfusion. However, TF expression and activity were significantly reduced in the vascular wall of TLR-4(-/-) mice compared with WT mice. In vivo, lipopolysaccharide accelerated the occlusion time in WT mice but not TLR-4(-/-) mice. In vitro, LPS-induced TF activity was reduced in endothelial cells of TLR-4(-/-) mice relative to WT mice. The data demonstrate that TLR-4 contributes to arterial thrombosis formation in vivo and causes increased TF expression and activity in vitro. The results further suggest that the stimulation is mainly derived by endothelial cells but is not due to platelet-derived TLR-4.

Copyright © 2014 the American Physiological Society.

KEYWORDS:

Toll-like receptor; arterial thrombosis; endothelial cells; platelet