| First Author | Banko NS | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 12 | Pages | 3394-404 |
| PubMed ID | 25451156 | Mgi Jnum | J:218258 |
| Mgi Id | MGI:5617088 | Doi | 10.1016/j.ajpath.2014.07.028 |
| Citation | Banko NS, et al. (2014) Glycogen synthase kinase 3alpha deficiency attenuates atherosclerosis and hepatic steatosis in high fat diet-fed low density lipoprotein receptor-deficient mice. Am J Pathol 184(12):3394-404 |
| abstractText | Studies have implicated signaling through glycogen synthase kinase (GSK) 3alpha/beta in the activation of pro-atherogenic pathways and the accelerated development of atherosclerosis. By using a mouse model, we examined the role of GSK3alpha in the development and progression of accelerated atherosclerosis. We crossed Gsk3a/GSK3alpha-knockout mice with low-density lipoprotein receptor (Ldlr) knockout mice. Five-week-old Ldlr(-/-);Gsk3a(+/+), Ldlr(-/-);Gsk3a(+/-), and Ldlr(-/-);Gsk3a(-/-) mice were fed a chow diet or a high-fat diet for 10 weeks and then sacrificed. GSK3alpha deficiency had no detectible effect on any measured parameters in chow-fed mice. High-fat-diet fed Ldlr(-/-) mice that were deficient for GSK3alpha had significantly less hepatic lipid accumulation and smaller atherosclerotic lesions (60% smaller in Ldlr(-/-);Gsk3a(+/-) mice, 80% smaller in Ldlr(-/-);Gsk3a(-/-) mice; P < 0.05), compared with Ldlr(-/-);Gsk3a(+/+) controls. GSK3alpha deficiency was associated with a significant increase in plasma IL-10 concentration and IL-10 expression in isolated macrophages. A twofold to threefold enhancement in endoplasmic reticulum stress-induced IL-10 expression was observed in Thp-1-derived macrophages that were pretreated with the GSK3alpha/beta inhibitor CT99021. Together, these results suggest that GSK3alpha plays a pro-atherogenic role, possibly by mediating the effects of endoplasmic reticulum stress in the activation of pro-atherogenic pathways. |
