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

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.