Platelet IκB Kinase-β Deficiency Increases Mouse Arterial Neointima Formation Via Delayed Glycoprotein Ibα Shedding

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2012 Dec 18

PMID 23241410

Citations 17

Authors

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

Affiliations

Soon will be listed here.

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(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.

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