title: Endothelial cells but not platelets are the major source of Toll-like receptor 4 in the arterial thrombosis and tissue factor expression in mice.
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.
authors.affiliation: Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.
authors.forename: Meiping
authors.initials: M
authors.lastname: Ren
authors.affiliation: Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.
authors.forename: Mao
authors.initials: M
authors.lastname: Luo
authors.affiliation: Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.affiliation: Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.
authors.forename: Kai
authors.initials: K
authors.lastname: Yan
authors.affiliation: Drug Discivery Research Center, Luzhou Medical College, Luzhou, Sichuan, China; and.
authors.forename: Min
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Drug 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.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000139:chemically induced; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D013925:Thromboplastin
keywords: Toll-like receptor; arterial thrombosis; endothelial cells; platelet