| Co-Investigator(Kenkyū-buntansha) |
HIGASHI Yusuke Teikyo Univ., Pharm. Sci., Res. Ass., 薬学部, 助手 (60286979)
MORI Masahiro Teikyo Univ., Pharm. Sci., Res. Ass., 薬学部, 助手 (00230079)
ITABE Hiroyuki Teikyo Univ., Pharm. Sci., Prof. Ass., 薬学部, 助教授 (30203079)
KIMURA Junji Terumo Ltd., Research Dev., Senior Res., 技術開発本部医薬品開発部門, 主任研究員
FUJIMOTO Yasuyuki Teikyo Univ., Pharm. Sci., Res. Ass., 薬学部, 助手 (60317724)
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| Research Abstract |
Our increasing knowledge of the atherogenic mechanisms of oxidation of LDL in the arterial wall, the clinical importance of circulating OxLDL is poorly understood, mainly because of a lack of a sensitive method to specifically detect circulating OxLDL levels. Although a number of investigators have measured thio-barbituric acid reactive substances in plasma, such as lipid hydroperoxides and isoprostanes, none have directly measured the formation of oxidatively modified LDL. Recently, immunoassays using murine monoclonal antibodies prepared against malondialdehyde-modified LDL (MDA-LDL) and against copper OxLDL demonstrated that circulating OxLDL or MDA-LDL exists in human plasma, and higher levels are found in patients with coronary heart disease (CHD). these studies, however, OxLDL was not distinguished from MDA-LDL because the monoclonal antibody against copper OxLDL cross-reacts against MDA-LDL. It is becoming clear that a large number of reactive lipid peroxidation products are generated in vivo during the oxidation of LDL. A study on apoE knockout mice, an animal model for the development of atherosclerosis, that auto-antibodies against OxLDL recognize different epitopes of complex structures formed during oxidation of lipoproteins or epitopes formed independently at different lesion sites.
We have developed a unique monoclonal antibody FOHla/DLH3 that reacts specifically against oxidized phosphatidylcholine (OxPC) by use of a homogenate of atheromatous plaques of human aorta as an antigen but not against native LDL, MDA-LDL, acetylated LDL, or glycated LDL. By use of this antibody in combination with an anti-apoprotein B antibody, an enzyme immunoassay of circulating OxLDL was developed. The present study, the clinical characteristics of plasma OxLDL levels in patients with atherosclerotic disease were investigated.
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