| Co-Investigator(Kenkyū-buntansha) |
KAIKITA Koichi Kumamoto University, School of Medicine, Assistant, 医学部, 教授 (30346978)
TERASAKI Yasuhiro Kumamoto University, School of Medicine, Assistant, 医学部, 助手 (50332870)
SAKASHITA Naomi Kumamoto University, School of Medicine, Assistant Prof., 医学部, 講師 (90284752)
SUZUKI Hiroshi Obihiro University of Agriculture and Veterinary Medicine, National Research Center for Protozoan Fiseases, Prof., 原虫病センター, 教授 (60333473)
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| Research Abstract |
Scavenger receptors (SRs) are a family of cell surface glycoproteins able to bind modified LDLs such as acetyiated LDL and oxidized LDL. Currently, SR family molecules are classified into six groups, namely class A to class F. Class A SR type I and type II(SR-AI,II) was the first SR to be cloned. In our previous study, SR-A I,II deficiency induced 60 % reduction of atherosclerotic lesions in atherpgenic ApoE-deficient mice of crossbred strains. To exdude the influence of crossbreeding, a new study using inbred C57BL/6J mice has been performed in me present project After 7 months of high fat diet, 70% reduction of lesion size was observed inSR-A I,II deficient C57BL/6J mice. On the other hand, administration of BO-653, a new antioxidant, has induced 75% size reduction in normal C57BL/6J mice. This fact indicated that anti-oxidant therapy is similarly or more effective in reducing atherogenesis compared to SR-AI,II deficiency.
To explore the effect of other types of SRs, we have studies the lesion development using a mouse strain that is deficient in a class E scavenger receptor, LOX-1 (lectin-like oxidized LDL receptor-1). So far, however, no significant difference in lesion size has been observed yet.
Concerning the study of LDL modification, we have found the complex formation of LDL and alpha-1-antitrypsin (AT) in human plasma. AT-LDL complex was found to be up taken by macrophages four times more rapidly than LDL. Since actual deposition of AT-LDL complex in human atherosclerotic lesion has been observed, suppression of AT-LDL formation and its deposition may reduce the development of atherosclerotic lesions.
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