Deletion of Myeloid GSK3α Attenuates Atherosclerosis and Promotes an M2 Macrophage Phenotype

Arteriosclerosis, Thrombosis, and Vascular Biology
Cameron S McAlpineGeoff H Werstuck

Abstract

Glycogen synthase kinase (GSK)-3α/β has been implicated in the pathogenesis of diabetes mellitus, cancer, Alzheimer, and atherosclerosis. The tissue- and homolog-specific functions of GSK3α and β in atherosclerosis are unknown. This study examines the effect of hepatocyte or myeloid cell deletion of GSK3α or GSK3β on atherosclerosis in low-density lipoprotein receptor (LDLR)(-/-) mice. We ablated GSK3α or GSK3β expression in hepatic or myeloid cells of LDLR(-/-) mice, and mice were fed a high-fat diet for 10 weeks. GSK3α or GSK3β deficiency in hepatic or myeloid cells did not affect metabolic parameters, including plasma lipid levels. Hepatic deletion of GSK3α or GSK3β did not affect the development of atherosclerosis or hepatic lipid content. Myeloid deletion of GSK3α, but not of GSK3β, reduced atherosclerotic lesion volume and lesion complexity. Mice lacking GSK3α in myeloid cells had a less inflammatory and more anti-inflammatory plasma cytokine profile. Macrophages within atherosclerotic lesions of myeloid GSK3α-deficient mice, but not of GSK3β-deficient mice, displayed reduced expression of markers associated with M1 macrophage polarization and enhanced expression of the M2 markers. Finally, bone marrow-derived macrophages...Continue Reading

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Citations

Jul 28, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Ziad Mallat
May 5, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Fang WangChangcheng Zhou
Jun 1, 2018·International Journal of Molecular Sciences·Aric HuangGeoff H Werstuck
Mar 30, 2019·Neural Plasticity·Ying BiLei Zhao
Dec 1, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Firdos Ahmad, James R Woodgett
Dec 20, 2020·Biomolecules·Octavio Silva-GarcíaVíctor M Baizabal-Aguirre
Apr 24, 2020·Atherosclerosis·Qiang WangYongjian Yang
Mar 7, 2021·International Journal of Molecular Sciences·Sarvatit Patel, Geoff H Werstuck
Feb 19, 2019·Biochemical Pharmacology·Masaki Arioka, Fumi Takahashi-Yanaga

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