title: Functions of monocyte chemotactic protein-3 in transgenic mice fed a high-fat, high-cholesterol diet.
abstract: Monocyte chemotactic protein-3 (MCP-3), a chemokine that is in a superfamily of structurally related small chemotactic cytokines involved in leukocyte trafficking, is regarded as a key factor in atherogenesis. In this study, we examined the changes in atherogenic parameters including hepatic lipid accumulation and oxidative balance in MCP- 3-overexpressing transgenic mice (MCP-3 mice) under atherogenic conditions. To induce an extreme atherogenic condition, mice were fed a high-fat, high-cholesterol (HFHC) diet for 12 weeks. The body weight and food intake were not changed by MCP-3 overexpression in the aorta. On a HFHC diet, the MCP-3 mice had higher plasma levels of total cholesterol and a higher atherogenic index compared with wild-type mice, although there were no differences in the plasma HDL-cholesterol and triglyceride levels. Furthermore, an increase in lipid accumulation was observed in the aortas as well as the livers of the HFHC diet-fed MCP-3 mice compared with wild-type mice. The activities of antioxidant enzymes increased in the livers of the HFHC diet-fed MCP-3 mice, whereas supplementation with antioxidants, naringin and hesperidin, reversed the activities of the hepatic antioxidant enzymes in HFHC diet-fed MCP-3 mice, indicating that there might be more oxidative damage to the tissues in the HFHC diet-fed MCP-3 mice leading to progression towards atherosclerosis and hepatic steatosis. Microarray analyses of the aorta revealed atherosclerosis-, PPARs-, lipoprotein receptor, and apolipoprotein-related genes that were affected by the HFHC diet in MCP-3 mice. These findings suggest that aortic MCP-3 overexpression may contribute to the development of atherosclerosis and hepatic steatosis under atherogenic conditions.
authors: School of Life Sciences and Biotechnology, Kyungpook National University Daegu 702-701, Korea.
authors: So Jung
authors: SJ
authors: An
authors: Un Ju
authors: UJ
authors: Jung
authors: Myung-Sook
authors: MS
authors: Choi
authors: Chan Kyu
authors: CK
authors: Chae
authors: Goo Taek
authors: GT
authors: Oh
authors: Yong Bok
authors: YB
authors: Park
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000737:chemistry / Q000473:pathology; D054410:Chemokine CCL7 / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat / Q000379:methods*; D015870:Gene Expression; D020869:Gene Expression Profiling; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis
chemical_list: D000975:Antioxidants; C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D008055:Lipids