Glycogen synthase kinase-3β is involved in C-reactive protein-induced endothelial cell activation

Abstract

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.

Spatial Multiplexed Protein Profiling of Cardiac Ischemia-Reperfusion Injury

“…GSK3-beta activation was shown to aggravate myocardial IRI. 25 Its dephosphorylation and activation by C-reactive protein was reported to promote EC activation, 52 and it mediated angiotensin II-induced endothelin expression in vascular ECs. 53 AMPK is a stress-responsive protein that protects against cardiomyocyte injury during IRI, mainly through maintaining mitochondrial function.…”