Platelet IB kinase- deficiency increases mouse arterial neointima formation via delayed glycoprotein Ib shedding. Academic Article uri icon

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-B is a critical molecule in platelet activation. Here, we investigated the role of the platelet nuclear factor-B 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 IB kinase- (IKK) (IKK(fl/fl)/PF4(cre)/LDLR(-/-)) and in control mice (IKK(fl/fl)/LDLR(-/-)). The size of the arterial neointima was 61% larger in the IKK(fl/fl)/PF4(cre)/LDLR(-/-) mice compared with the littermate control IKK(fl/fl)/LDLR(-/-) mice. Compared with the control mice, the IKK(fl/fl)/PF4(cre)/LDLR(-/-) mice exhibited more leukocyte adhesion at the injured area. The extent of glycoprotein Ib shedding after platelet activation was compromised in the IKK-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 Ib shedding in activated IKK-deficient platelets. CONCLUSIONS: Platelet IKK deficiency increases the formation of injury-induced arterial neointima formation. Thus, nuclear factor-B-related inhibitors should be carefully evaluated for use in patients after an arterial intervention.

published proceedings

  • Arterioscler Thromb Vasc Biol

altmetric score

  • 0.5

author list (cited authors)

  • Wei, S., Wang, H., Zhang, G., Lu, Y., An, X., Ren, S., ... Huo, Y.

citation count

  • 18

complete list of authors

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

publication date

  • February 2013