1990 Fiscal Year Annual Research Report

粥状動脈硬化症の成因に関する基礎的研究

Research Project

Project/Area Number	01304063
Research Institution	Kyoto University
Principal Investigator	北徹京都大学, 医学部, 教授 (60161460)
Co-Investigator(Kenkyū-buntansha)	山本徳男東北大学, 遺伝子実験施設, 助教授山田信博東京大学, 医学部, 助手 (40200729) 斎藤康千葉大学, 医学部, 講師 (50101358) 堀内正公熊本大学, 医学部, 講師成宮周京都大学, 医学部, 助教授 (70144350)
Keywords	血管内皮細胞 / 泡沫細胞 / 平滑筋細胞 / 酸化LDL / リポタンパクリパ-ゼ / 動脈硬化
Research Abstract	我々は今回のプロジェクト研究を通じて、血中に増加したLDLが如何なる機構で血管内皮細胞障害、マクロファ-ジの泡沫化およびその集簇、さらには、血管平滑筋細胞の増殖、あるいは遊走を引き起こすかにつき、種々の分野の専門家と共同研究を行いつつある。北、堀内は酸化LDL、あるいはアセチルLDLのマクロファ-ジへの取り込み機序について研究を進めており、その受容体の諸性質を明らかにしつつある。また、泡沫細胞の脱泡沫化についても、HDLの役割、さらに酸化変性を受けた酸化HDLの脱泡沫化における影響について検討を加えている(PNAS投稿中)。北等は、抗酸化剤であるプロブコ-ルがマクロファ-ジを活性化することを、ボイデンチャンバ-法を用いて明らかにした(投稿準備中)。また、成宮、北等はマクロファ-ジが泡沫化するとプロスタグランディンE_2の産生が抑制されることを見い出したが、ホスホリパ-ゼA_2の活性低下が原因であることを見い出し、検討中である。斎藤等は彼らの見い出した平滑筋細胞遊走因子、増殖因子の単離、精製を行っている。山田等はリポタンパクリパ-ゼの遺伝子解析から、リパ-ゼ欠損症の患者の遺伝子解析を行っているが、最近スプライシング異常により惹起される症例を発見した。現在、さらにマクロファ-ジのリポタンパクリパ-ゼの合成調節の解析を進行中である。山本は、WHHLサウギの病変部位の遺伝子解析を行っているが、最近ある特定の遺伝子産物が病変部に限り発現していることを見い出し、この解析を進めている。この様に、本年度の研究は順調に進んでおり、次年度以降の成果が待たれる。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] O'Brien,K.,Nagano,Y.,Gown,A.,Kita,T.& Chait,A.: "Probucol treatment affects the cellular composition but not antiーoxidized LDL immunoreactivity of plaques from Watanabe heritable hyperlipidemic rabbits." Arteriosclerosis. (1991)
[Publications] Kume,N.,Arai,H.,Kawai,C.& Kita,T.: "Receptors for modified lowーdensity lipoproteins on human endothelial cells:different recognition for acetylated lowーdensity lipoprotein and oxidized lowーdensity lipoprotein." Biochim.Biophys.Acta. 1091. 63-67 (1991)
[Publications] Kita,T.,Ishii,K.,Yokode,M.,Kume,N.,Nagano,Y.,Arai,H.& Kawai,C.: "The role of oxidized low density lipoprotein in the pathogenesis of atherosclerosis." European Heart Journal. 11. 122-127 (1990)
[Publications] Kita,T.,Yokode,M.,Ishii,K.,Arai,H.& Nagano,Y.: "The role of atherogenic low density lipoproteins(LDL)in the pathogenesis of atherosclerosis." Ann.New York Acad.Sci.598. 188-193 (1990)
[Publications] Morii,N.,Kawano,K.,Sekine,A.,Yamada,T.,& Narumiya S.: "Purification of GTPase activating protein specific for the <rho>___ー gene products." J.Biol.Chem.(1991)
[Publications] Hirata,M.,Hayashi,Y.,Ushikubi,F.,Yokota,Y.,Kageyama,R.,Nakanishi,S.& Narumiya,S.: "Cloning and expression of cDNA for a human thromboxane A_2 receptor." Nature. (1991)
[Publications] Rahim,A.T.M.A.,Miyazaki,A.,morino,Y.& Horiuchi,S.: "Biochemical demonstration of endocytosis and subsequent resecretion of high density lipoprotein by rat peritoneal macrophages." Biochim.Biophys.Acta. (1991)
[Publications] Miyazaki,A.,Rahim,A.T.M.A.,Araki,S.,Morino,Y.& Horiuchi,S.: "Chemical crossーlinking alters high density lipoporotein to be recognized by a scavenger receptor in rat peritoneal macrophages." Biochim.Biophys.Acta. (1991)
[Publications] Horiuchi,S.,Araki,N.& Morino,Y.: "Immunochemical approach to characterize advanced glycation end products of Maillard reaction;Evidence for the presence of a common structure." J.Biol.Chem.(1991)
[Publications] Koyama,N.,Koshikawa,T.,Morisaki,N.,Saito,Y.& Yoshida,S.: "Bifunctional effects of transforming growth factorーβ on migration of cultured rat aortic smooth muscle cells." Biochem.Biophys.Res.Commun.169. 725-729 (1990)
[Publications] Saito,Y.,Morisaki,N.& Koyama,N.: "Autocrine system for smooth muscle cell migration and proliferation in the arterial wall." Ann.New York Acad.Sci.598. 194-199 (1990)
[Publications] Koyama,N.,Koshikawa,T.,Morisaki,N.,Saito,Y.& Yoshida,S.: "Secretion of a potent new migration factor for smooth muscle cells (SMC) by cultured SMC." Atherosclerosis.
[Publications] Ishibashi,S.,Yamada,N.,Shimano,H.,Mori,N.,Mokuno,H.,Gotohda,T.,Kawakami,M.,Murase,T.& Takaku,F.: "Apolipoprotein E and lipoprotein lipase secreted from human monocyteーderived macrophages modulate VLDL uptake." J.Biol.Chem.265. 3040-3047 (1990)
[Publications] Shimano,H.,Yamada,N.,Ishibashi,S.,Harada,K.,Matsumoto,A.,Mori,N.,Inaba,T.,Itakura,H.,Motoyoshi,K.& Takaku,F.: "Human monocyteーcolony stimulating factor enhances the clearance of lipoproteins containing apo B 100 via both LDL receptorーdependent and ーindependent pathways in rabbit." J.Biol.Chem.265. 12869-12875 (1990)
[Publications] Ishibashi,S.,Inaba,T.,Shimano,H.,Harada,K.,Inoue,I.,Mokuno,H.,Mori,N.,Gotohda,T.,Takaku,F.& Yamada,N.: "Monocyte colonyーstimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocyteーderived macrophages." J.Biol.Chem.265. 14109-14117 (1990)
[Publications] Suzuki,H.,Kawarabayasi,Y.,Kondo,J.,Abe,T.,Nishikawa,K.,Kimura,S.,Hashimoto,T.& Yamamoto T.: "Structure and regulation of rat longーchain acylーCoA synthetase." J.Biol.Chem.265. 8681-8685 (1990)

1990 Fiscal Year Annual Research Report

粥状動脈硬化症の成因に関する基礎的研究

Principal Investigator

北 徹 京都大学, 医学部, 教授 (60161460)

Research Products

[Publications] O'Brien,K.,Nagano,Y.,Gown,A.,Kita,T.& Chait,A.: "Probucol treatment affects the cellular composition but not antiーoxidized LDL immunoreactivity of plaques from Watanabe heritable hyperlipidemic rabbits." Arteriosclerosis. (1991)

[Publications] Kume,N.,Arai,H.,Kawai,C.& Kita,T.: "Receptors for modified lowーdensity lipoproteins on human endothelial cells:different recognition for acetylated lowーdensity lipoprotein and oxidized lowーdensity lipoprotein." Biochim.Biophys.Acta. 1091. 63-67 (1991)

[Publications] Kita,T.,Ishii,K.,Yokode,M.,Kume,N.,Nagano,Y.,Arai,H.& Kawai,C.: "The role of oxidized low density lipoprotein in the pathogenesis of atherosclerosis." European Heart Journal. 11. 122-127 (1990)

[Publications] Kita,T.,Yokode,M.,Ishii,K.,Arai,H.& Nagano,Y.: "The role of atherogenic low density lipoproteins(LDL)in the pathogenesis of atherosclerosis." Ann.New York Acad.Sci.598. 188-193 (1990)

[Publications] Morii,N.,Kawano,K.,Sekine,A.,Yamada,T.,& Narumiya S.: "Purification of GTPase activating protein specific for the <rho>___ー gene products." J.Biol.Chem.(1991)

[Publications] Hirata,M.,Hayashi,Y.,Ushikubi,F.,Yokota,Y.,Kageyama,R.,Nakanishi,S.& Narumiya,S.: "Cloning and expression of cDNA for a human thromboxane A_2 receptor." Nature. (1991)

[Publications] Rahim,A.T.M.A.,Miyazaki,A.,morino,Y.& Horiuchi,S.: "Biochemical demonstration of endocytosis and subsequent resecretion of high density lipoprotein by rat peritoneal macrophages." Biochim.Biophys.Acta. (1991)

[Publications] Miyazaki,A.,Rahim,A.T.M.A.,Araki,S.,Morino,Y.& Horiuchi,S.: "Chemical crossーlinking alters high density lipoporotein to be recognized by a scavenger receptor in rat peritoneal macrophages." Biochim.Biophys.Acta. (1991)

[Publications] Horiuchi,S.,Araki,N.& Morino,Y.: "Immunochemical approach to characterize advanced glycation end products of Maillard reaction;Evidence for the presence of a common structure." J.Biol.Chem.(1991)

[Publications] Koyama,N.,Koshikawa,T.,Morisaki,N.,Saito,Y.& Yoshida,S.: "Bifunctional effects of transforming growth factorーβ on migration of cultured rat aortic smooth muscle cells." Biochem.Biophys.Res.Commun.169. 725-729 (1990)

[Publications] Saito,Y.,Morisaki,N.& Koyama,N.: "Autocrine system for smooth muscle cell migration and proliferation in the arterial wall." Ann.New York Acad.Sci.598. 194-199 (1990)

[Publications] Koyama,N.,Koshikawa,T.,Morisaki,N.,Saito,Y.& Yoshida,S.: "Secretion of a potent new migration factor for smooth muscle cells (SMC) by cultured SMC." Atherosclerosis.

[Publications] Ishibashi,S.,Yamada,N.,Shimano,H.,Mori,N.,Mokuno,H.,Gotohda,T.,Kawakami,M.,Murase,T.& Takaku,F.: "Apolipoprotein E and lipoprotein lipase secreted from human monocyteーderived macrophages modulate VLDL uptake." J.Biol.Chem.265. 3040-3047 (1990)

[Publications] Suzuki,H.,Kawarabayasi,Y.,Kondo,J.,Abe,T.,Nishikawa,K.,Kimura,S.,Hashimoto,T.& Yamamoto T.: "Structure and regulation of rat longーchain acylーCoA synthetase." J.Biol.Chem.265. 8681-8685 (1990)

北徹京都大学, 医学部, 教授 (60161460)