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Atherosclerosis and Lipoproteins |
From the Department of Cardiovascular Medicine (E.T., H.S., H.K., Y.E., Y.M., K.M., G.K., K.E., A.T.), Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Department of Internal Medicine (M.Y.), Kumamoto University, Kumamoto, Japan; Department of Pathology (O.T.), Saga Medical School, Saga, Japan; and Institute for Experimental Animals (M.S.), Kobe University School of Medicine, Kobe, Japan.
Consulting Editor for this article was Alan M. Fogelman, MD, Professor of Medicine and Executive Chair, Departments of Medicine and Cardiology, UCLA School of Medicine, Los Angeles, Calif.Correspondence to Hiroaki Shimokawa, MD, PhD, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-82, Japan. E-mail shimo{at}cardiol.med.kyushu-u.ac.jp
Objective This study was designed to examine why in WHHL rabbits, muscular arteries, such as the carotid artery, are relatively resistant to atherosclerosis compared with the aorta, with a special reference to monocyte chemoattractant protein (MCP)-1.
Methods and Results MCP-1 mRNA expression was quantitated by Northern blot analysis, and its protein expression was quantitated by immunostaining and ELISA at the age of 1, 3, 6, and 12 months (n=5 to 6 each). In the aorta, atherosclerotic lesions were progressively developed with aging, and MCP-1 was highly expressed in endothelial cells and infiltrating macrophages. By contrast, in the carotid artery, atherosclerotic lesions and MCP-1 immunoreactivity were not evident throughout the experimental period. Unexpectedly, however, the extent of MCP-1 mRNA expression was comparable between the aorta and the carotid artery throughout the experimental period. Endothelial cells in primary culture from the aorta and the carotid artery expressed the same extent of MCP-1 mRNA on stimulation by oxidized LDL. There was no abnormality in primary structure of MCP-1 cDNA in WHHL.
Conclusions These results suggest that in WHHL, the atherosclerosis process, including MCP-1 protein expression, may be reduced in the carotid artery (and possibly in other muscular arteries), accounting in part for the regional resistance to atherosclerosis.
Key Words: atherosclerosis chemokines gene expression monocyte chemoattractant protein-1 WHHL
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