| First Author | Wei S | Year | 2013 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 33 |
| Issue | 2 | Pages | 241-8 |
| PubMed ID | 23241410 | Mgi Jnum | J:216903 |
| Mgi Id | MGI:5609920 | Doi | 10.1161/ATVBAHA.112.300781 |
| Citation | Wei S, et al. (2013) Platelet IkappaB kinase-beta deficiency increases mouse arterial neointima formation via delayed glycoprotein Ibalpha shedding. Arterioscler Thromb Vasc Biol 33(2):241-8 |
| abstractText | 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-kappaB is a critical molecule in platelet activation. Here, we investigated the role of the platelet nuclear factor-kappaB 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 IkappaB kinase-beta (IKKbeta) (IKKbeta(fl/fl)/PF4(cre)/LDLR(-/-)) and in control mice (IKKbeta(fl/fl)/LDLR(-/-)). The size of the arterial neointima was 61% larger in the IKKbeta(fl/fl)/PF4(cre)/LDLR(-/-) mice compared with the littermate control IKKbeta(fl/fl)/LDLR(-/-) mice. Compared with the control mice, the IKKbeta(fl/fl)/PF4(cre)/LDLR(-/-) mice exhibited more leukocyte adhesion at the injured area. The extent of glycoprotein Ibalpha shedding after platelet activation was compromised in the IKKbeta-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 Ibalpha shedding in activated IKKbeta-deficient platelets. CONCLUSIONS: Platelet IKKbeta deficiency increases the formation of injury-induced arterial neointima formation. Thus, nuclear factor-kappaB-related inhibitors should be carefully evaluated for use in patients after an arterial intervention. |
