Platelet IκB kinase-β deficiency increases mouse arterial neointima formation via delayed glycoprotein ibα shedding

Shujian Wei, Huan Wang, Guoying Zhang, Ying Lu, Xiaofei An, Shumei Ren, Yunmei Wang, Yuguo Chen, James G. White, Chunxiang Zhang, Daniel I. Simon, Chaodong Wu, Zhenyu Li, Yuqing Huo

Research output: Contribution to journalArticle

14 Scopus citations

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. METHODS AND 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/PF4/LDLR) and in control mice (IKKβ/LDLR). The size of the arterial neointima was 61% larger in the IKKβ/PF4/LDLR mice compared with the littermate control IKKβ/LDLR mice. Compared with the control mice, the IKKβ/PF4/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. CONCLUSION-: 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.

Original languageEnglish (US)
Pages (from-to)241-248
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2013

Keywords

  • NF-κB
  • arterial injury
  • leukocytes
  • platelets
  • restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Wei, S., Wang, H., Zhang, G., Lu, Y., An, X., Ren, S., Wang, Y., Chen, Y., White, J. G., Zhang, C., Simon, D. I., Wu, C., Li, Z., & Huo, Y. (2013). Platelet IκB kinase-β deficiency increases mouse arterial neointima formation via delayed glycoprotein ibα shedding. Arteriosclerosis, thrombosis, and vascular biology, 33(2), 241-248. https://doi.org/10.1161/ATVBAHA.112.300781