title: Platelet IκB kinase-β deficiency increases mouse arterial neointima formation via delayed glycoprotein Ibα shedding.
abstract: OBJECTIVE
  On the luminal surface of injured arteries, platelet activation and leukocyte-platelet interactions are critical for the initiation and progression of arterial restenosis. The transcription factor nuclear factor-κB is a critical molecule in platelet activation. Here, we investigated the role of the platelet nuclear factor-κB pathway in forming arterial neointima after arterial injury.
  
  
  RESULTS
  We performed carotid artery wire injuries in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice with a platelet-specific deletion of IκB kinase-β (IKKβ) (IKKβ(fl/fl)/PF4(cre)/LDLR(-/-)) and in control mice (IKKβ(fl/fl)/LDLR(-/-)). The size of the arterial neointima was 61% larger in the IKKβ(fl/fl)/PF4(cre)/LDLR(-/-) mice compared with the littermate control IKKβ(fl/fl)/LDLR(-/-) mice. Compared with the control mice, the IKKβ(fl/fl)/PF4(cre)/LDLR(-/-) mice exhibited more leukocyte adhesion at the injured area. The extent of glycoprotein Ibα shedding after platelet activation was compromised in the IKKβ-deficient platelets. This effect was associated with a low level of the active form of A Disintegrin And Metalloproteinase 17, the key enzyme involved in mediating glycoprotein Ibα shedding in activated IKKβ-deficient platelets.
  
  
  CONCLUSIONS
  Platelet IKKβ deficiency increases the formation of injury-induced arterial neointima formation. Thus, nuclear factor-κB-related inhibitors should be carefully evaluated for use in patients after an arterial intervention.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of Emergency, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Shujian
authors.initials: S
authors.lastname: Wei
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiaofei
authors.initials: X
authors.lastname: An
authors.forename: Shumei
authors.initials: S
authors.lastname: Ren
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Chen
authors.forename: James G
authors.initials: JG
authors.lastname: White
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Simon
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000072198:ADAM17 Protein; D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000201:enzymology*; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion; D004195:Disease Models, Animal; D051550:I-kappa B Kinase / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058426:Neointima; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011485:Protein Binding; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D057772:Vascular System Injuries / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D016177:Macrophage-1 Antigen; D019038:Platelet Glycoprotein GPIb-IX Complex; D011973:Receptors, LDL; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; D051722:ADAM Proteins; D000072198:ADAM17 Protein