Myeloid GSK3α Deficiency Reduces Lesional Inflammation and Neovascularization during Atherosclerotic Progression.

The molecular mechanisms by which cardiovascular risk factors promote the development of atherosclerosis are poorly understood. We have recently shown that genetic ablation of myeloid glycogen synthase kinase (GSK)-3α attenuates atherosclerotic lesion development in low-density lipoprotein receptor-deficient (Ldlr-/-) mice. However, the precise contributions of GSK3α/β in atherogenesis are not known. The aim of this study is to investigate the effect of GSK3α and/or β deficiency on lesional inflammation and plaque vascularization. Five-week-old female Ldlr-/- mice were fed a high-fat diet for 10 weeks to establish atherosclerotic lesions. Mice were harvested at 15 weeks of age and atherosclerotic lesions were characterized. The results indicate that, in addition to significantly reducing plaque volume, GSK3α-deficiency decreases inflammation, reduces vasa vasorum density at the aortic sinus, and reduces plasma c-reactive protein (CRP) levels. GSK3β-deficiency is associated with decreased plasma CRP levels but does not affect lesional inflammation or vascularization. These results suggest GSK3α may be an applicable target for the development of novel anti-atherogenic therapies.

Myeloid GSK3α Deficiency Reduces Lesional Inflammation and Neovascularization during Atherosclerotic Progression. Journal Articles