Macrophage proliferation in atherosclerosis |
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Authors: | Sakai M Kobori S Miyazaki A Horiuchi S |
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Affiliation: | Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan. |
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Abstract: | Oxidized LDL can induce an increase in intracellular calcium concentration and the activation of protein kinase C in mouse peritoneal macrophages. The activation of protein kinase C leads to the release into the culture medium of granulocyte-macrophage colony-stimulating factor, which plays a priming role in oxidized LDL-induced macrophage proliferation. The expression of granulocyte-macrophage colony-stimulating factor in macrophages by oxidized LDL is positively regulated in the 5'-flanking region of granulocyte-macrophage colony-stimulating factor gene from sequence -169 to -160, but negatively regulated from -91 to -82. Granulocyte-macrophage colony-stimulating factor released by oxidized LDL from macrophages induces proliferation in autocrine or paracrine fashion via the activation of phosphatidylinositol 3-kinase. The capacity of oxidized LDL to induce macrophage proliferation in vitro may be involved in the enhanced progression of atherosclerosis in vivo. |
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