2Department of Cardiology, Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Guangzhou, 510260, PR China; fax: 86-20-3415-3566; E-mail: firstname.lastname@example.org
* To whom correspondence should be addressed.
Received February 6, 2013; Revision received April 11, 2013
C-reactive protein (CRP) is a significant contributor to atherosclerosis and a powerful predictor of cardiovascular risk. The role of CRP in endothelial cell (EC) activation has been extensively investigated, but the underlying mechanisms have not been fully elucidated. The effect of glycogen synthase kinase-3β (GSK-3β) on CRP-induced EC activation was evaluated in this study. We observed that CRP decreased endothelial nitric oxide synthase (eNOS) activity during EC activation. CRP also activated GSK-3β by dephosphorylating its Ser9 level and reducing β-catenin protein expression in a time-dependent manner. We also found that the GSK-3β inhibitors TDZD-8 and SB415286 partially restored eNOS activity and suppressed the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. These data provide new evidence for the involvement of GSK-3β in EC activation.
KEY WORDS: GSK-3β, CRP, endothelial activation, eNOS, atherosclerosis