1993 Fiscal Year Final Research Report Summary
A novel monoclonal antibody recognizing extracellular space of the atherosclerotic lesions in WHHL rabbits.
| Project/Area Number |
03454495
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
TAKANO Tatsuya Teikyo Univ., Fac. of Pharm. Sci., Professor, 薬学部, 教授 (40124995)
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| Co-Investigator(Kenkyū-buntansha) |
EYA Seiji Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (20221814)
MORI Masahiro Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (00230079)
ITABE Hiroyuki Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (30203079)
MINEO Chieko Teikyo Univ., Fac. of Pharm. Sci., Research Associate, 薬学部, 助手 (00190710)
IMANAKA Tsuneo Teikyo Univ., Fac. of Pharm. Sci., Assistant Professor, 薬学部, 講師 (50119559)
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| Project Period (FY) |
1991 – 1993
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| Keywords | atherosclerosis / glycoprotein / vitronectin / extracellular matrix / cholesterol |
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| Research Abstract |
In order to study the mechanisms of cholesteryl ester accumulation in the extracellular space of the atherosclerotic aorta, we prepared novel monoclonal antibodies against atherosclerotic lesions using a delipidated crude homogenate of atherosclerotic aorta from Watanabe-heritable hyperlipidemic (WHHL) rabbits as a complex mixture of immunogens. By screening the antibodies histochemically, we were able to obtain for the first time monoclonal antibodies which specifically recognized the extracellular matrix with lipid-laden deposits (EMRla/212D) in atherosclerotic lesions. The purified antigenic material is a glycoprotein with a molecular mass of 66 kDa, and the epitope of the antigenic material contains sialic acid as a major element.
We have isolated from rabbit liver cDNA library clones coding for the 66-kDa glycoprotein (GP66). The clone spans the sequence coding for the entire GP66 (456 amino acids) and 19 amino acids of a signal peptide. GP66 was deduced to be rabbit vitronectin from its nucleotide sequence, containing an Arg-Gly-Asp cell attachment sequence and showing 76% amino acid sequence homology with human vitronectin. Furthermore, EMRla/212D recognized rabbit vitronectin purified by heparin affinity chromatography. RNA blot hybridization detected one transcript of the same size in normal and WHHL rabbit liver. The levels of plasma GP66 and liver GP66 mRNA were not altered, whereas 9-fold greater accumulation of GP66 was observed in the thoracic aorta of WHHL rabbit. These results suggest that GP66 is rabbit vitronectin, which selectively accumulates in the atherosclerotic aorta with the development of atherosclerosis.
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[Publications] Magari, K., Fukushima, H., Ishimaru, S., Furukawa, K, Yagyu, Y.and Takano, T.: "Platelet adhesion to a biomimetic prosthesis prepared from canine arterial wall." Artif. Organs. 15(6). 492-497 (1991)
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[Publications] Yagyu, Y., Hashida, R., Iwasaki, K., Mineo, C., Imanaka, T.and Takano, T.: "Effect of PGI_2 on platelet binding to partially denuded endothelial monolayr in vitro." Thromb. Res.64. 733-744 (1991)
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