1993 Fiscal Year Final Research Report Summary

動脈硬化症の分子生物学的解析と予防・抑制対策に関する総合的研究

Research Project

Project/Area Number	04304051
Research Category	Grant-in-Aid for Co-operative Research (A)
Allocation Type	Single-year Grants
Research Field	内分泌・代謝学
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, 教授 (30192412) 堀内正公熊本大学, 医学部, 教授 (10117377) 山田信博東京大学, 医学部, 助手 (40200729) 松沢佑次大阪大学, 医学部, 教授 (70116101) 高井義美神戸大学, 医学部, 教授 (60093514)
Project Period (FY)	1992 – 1993
Keywords	リゾフォスファチジルコリン / マクロファージ / M-CSF / CETP / コレステロール逆転送系 / SDMF / Rho / VLDL受容体
Research Abstract	動脈硬化症の分子生物学的解析と予防抑制対策に対する総合的研究をめざすわれわれの研究は順調に進みつつある。 1)血管内皮細胞障害、あるいは活性化 LDLの酸化過程で生ずるリゾフォスファチジルコリン(LPC)が内皮細胞においてVCAM1の発現を誘導すること、更にそれがPKCを関与しない機構で行われることを明らかにした。 2)マクロファージの泡沫化脱泡沫化 M-CSFがマクロファージのACATならびにコレステロールエステル加水分解酵素機能を調節することによりコレステロールエステル蓄積の制御に関わる可能性が示された。またその脱泡沫化にはHDLとマクロファージの相互作用がならびにCETPを介したコレステロール逆転送系の関与が考えられるが、その分子機構についても検討中ある。 3)平滑細胞の増殖と移動の分子機構 SDMF(平滑筋細胞由来遊走因子)の精製に引き続きその構造決定が行われている。またsmall GTP結合蛋白であるRhoが平滑筋細胞の血管内における移動に関わることが明らかにされた。 4)動脈硬化惹起遺伝子 VLDL受容体蛋白ならびに遺伝子の構造決定にもとづき、その粥状動脈硬化形成過程における意義の解析が行われている。

Research Products
(13 results)

All Other

All Publications (13 results)

[Publications] Kita,T.,et al.: "Cigarette smoke,LDL and cholesteryl ester accumulation in macrophages." Ann.N.Y.Acad.Sci.686. 91-98 (1993)
[Publications] Ueda,Y.,et al.: "Different expression of modified low density lipoprotein receptors in rabbit peritoneal macropahges and K upffer cells." Atherosclerosis. 101. 25-35 (1993)
[Publications] Tanaka,M.,et al.: "Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholesteryl ester contents in rabbit hepatocytes." J.Biol.Chem.268. 12713-12718 (1993)
[Publications] Takaishi,K.,et al.: "Involvement of Rho p21 small GTP-binding protein and its regulator in the HGF-induced cell motility." Oncogene. 9. 273-279 (1993)
[Publications] Kishi,K.,et al.: "Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP-GTP exchange protein(rho GDI)." J.Cell Biol.120. 1187-1195 (1993)
[Publications] Hiraoka,H.,et al.: "Decrease of hepatic triglyceride lipase levels and increase of cholesteryl ester transfer protein levels in patients with primary biliary cirrhosis:Relationship abnormalities in high-density lipoprotein." Hepatology. 18. 103-110 (1993)
[Publications] Takahashi,K.,et al.: "Amissense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins." J.Clin.Invest.92. 2060-2064 (1993)
[Publications] Shimada,M.,et al.: "Overexpression of human lipoprotein lipase in transgenic mice." J.Biol.Chem.268. 17924-17929 (1993)
[Publications] Inaba,T.,et al.: "Expression of platelet-derived growth factor βreceptor on human monocyte-derived macrophages and effects of platelet-derived growth factor BB dimer on the cellular function." J.Biol.Chem.268. 24353-24360 (1993)
[Publications] Koyama,N.,et al.: "Purification and characterization of an autocrine migration factor for vascular smooth muscle cells(SMC),MC-derived migration factor." J.Biol.Chem.268. 13301-13308 (1993)
[Publications] Yokote,K.,et al.: "The phospholipase-A_2 reaction leads to increased monocyte adhesion of endothelial cells via the expression of adhesion molecules" Eur.J.Biochem.217. 723-729 (1993)
[Publications] Yui,S.,et al.: "Induction of murine macrophage growth by modified LDLs." Ateriosclerosis and Thrombosis. 13. 331-337 (1993)
[Publications] Miyata,T.,et al.: "β2-microglobulin modified with advanced glycation end products is a major component of hemodialysis-aassociated amyloidosis." J.Clin.Invest.92. 1243-1252 (1993)

1993 Fiscal Year Final Research Report Summary

動脈硬化症の分子生物学的解析と予防・抑制対策に関する総合的研究

Principal Investigator

北 徹 京都大学, 医学部, 教授 (60161460)

Research Products

[Publications] Kita,T.,et al.: "Cigarette smoke,LDL and cholesteryl ester accumulation in macrophages." Ann.N.Y.Acad.Sci.686. 91-98 (1993)

[Publications] Ueda,Y.,et al.: "Different expression of modified low density lipoprotein receptors in rabbit peritoneal macropahges and K upffer cells." Atherosclerosis. 101. 25-35 (1993)

[Publications] Tanaka,M.,et al.: "Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholesteryl ester contents in rabbit hepatocytes." J.Biol.Chem.268. 12713-12718 (1993)

[Publications] Takaishi,K.,et al.: "Involvement of Rho p21 small GTP-binding protein and its regulator in the HGF-induced cell motility." Oncogene. 9. 273-279 (1993)

[Publications] Kishi,K.,et al.: "Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP-GTP exchange protein(rho GDI)." J.Cell Biol.120. 1187-1195 (1993)

[Publications] Hiraoka,H.,et al.: "Decrease of hepatic triglyceride lipase levels and increase of cholesteryl ester transfer protein levels in patients with primary biliary cirrhosis:Relationship abnormalities in high-density lipoprotein." Hepatology. 18. 103-110 (1993)

[Publications] Takahashi,K.,et al.: "Amissense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins." J.Clin.Invest.92. 2060-2064 (1993)

[Publications] Shimada,M.,et al.: "Overexpression of human lipoprotein lipase in transgenic mice." J.Biol.Chem.268. 17924-17929 (1993)

[Publications] Inaba,T.,et al.: "Expression of platelet-derived growth factor βreceptor on human monocyte-derived macrophages and effects of platelet-derived growth factor BB dimer on the cellular function." J.Biol.Chem.268. 24353-24360 (1993)

[Publications] Koyama,N.,et al.: "Purification and characterization of an autocrine migration factor for vascular smooth muscle cells(SMC),MC-derived migration factor." J.Biol.Chem.268. 13301-13308 (1993)

[Publications] Yokote,K.,et al.: "The phospholipase-A_2 reaction leads to increased monocyte adhesion of endothelial cells via the expression of adhesion molecules" Eur.J.Biochem.217. 723-729 (1993)

[Publications] Yui,S.,et al.: "Induction of murine macrophage growth by modified LDLs." Ateriosclerosis and Thrombosis. 13. 331-337 (1993)

[Publications] Miyata,T.,et al.: "β2-microglobulin modified with advanced glycation end products is a major component of hemodialysis-aassociated amyloidosis." J.Clin.Invest.92. 1243-1252 (1993)

北徹京都大学, 医学部, 教授 (60161460)