title: Inhibition of reactive oxygen species generation attenuates TLR4-mediated proinflammatory and proliferative phenotype of vascular smooth muscle cells.
abstract: Reactive oxygen species (ROS) are associated with inflammation and vasculature dysfunction. This study aimed to investigate the potential role of the ROS on vascular Toll-like receptor 4 (TLR4)-mediated proinflammatory and proliferative phenotype of vascular smooth muscle cells (VSMCs). A wire-induced carotid injury model was used in male TLR4-deficient (TLR4(-/-)) and wild-type C57BL/6J mice to induce neointima formation. In the presence or absence of the ROS scavenger apocynin for 14 days, increased TLR4 and proinflammatory cytokines were observed in wire injury-induced carotid neointima and in platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMCs. The TLR4(-/-) protected the injured carotid from neointimal formation and impaired the cellular proliferation and migration in response to PDGF-BB. Apocynin attenuated intimal hyperplasia. Pre-treatment with apocynin significantly inhibited intracellular ROS generation, accompanied by a significant suppression of TLR4 and proinflammatory cytokines expression, and VSMC proliferation and migration. However, the results were not obvious in TLR4(-/-) condition. These findings highlight the importance of ROS inhibition in TLR4-mediated proinflammatory and proliferative phenotype of VSMCs, and suggest ROS as an essential therapeutic target for TLR4-associated vascular inflammation and vascular diseases.
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pi
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
authors.forename: Bing-Hu
authors.initials: BH
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Guo
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Cao
authors.forename: Chang-Yue
authors.initials: CY
authors.lastname: Gao
authors.forename: Jing-Cheng
authors.initials: JC
authors.lastname: Li
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D058426:Neointima / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D020574:Proto-Oncogene Proteins c-sis; D017382:Reactive Oxygen Species; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077214:Becaplermin; C056165:acetovanillone