1996 年度実績報告書

動脈硬化の分子機構

研究課題

研究課題/領域番号	08357011
研究機関	京都大学
研究代表者	北徹京都大学, 医学研究科, 教授 (60161460)
研究分担者	渋谷正史東京大学, 医科学研究所, 教授 (10107427) 松沢佑次大阪大学, 医学部, 教授 (70116101) 丸山征郎鹿児島大学, 医学部, 教授 (20082282) 永井良三群馬大学, 医学部, 教授 (60207975) 佐藤靖史東北大学, 加齢医学研究所, 教授 (50178779)
キーワード	血管形成 / 血管新生 / ずり応力 / 酸化LDL / 血管内皮細胞障害 / 血管平滑筋細胞増殖 / 動脈硬化 / マクロファージ
研究概要	動脈硬化は、血管内皮細胞障害(活性化)と血液細胞の相互連関、さらに血管平滑筋細胞の形質変換、脱分化が中心病態をなし、血管構築(血管形成、ならびに血管新生)の機構と類似の普遍的な分子機構の関与が強く示唆されている。従って、動脈硬化の分子機構を探求する上で立脚すべき最も基本的な命題につき検討を加え、 1)血管機構の分子機構、 2)血管内皮細胞障害と血管細胞、 3)血管平滑筋細胞形質変換と脱分化、の3テーマに焦点を絞り、それぞれのデ-マを計画班として、I、II、III班とした。さらに、それらを調整総括推進するために、総括班を設けた。そこで「動脈硬化の分子機構」の推進のため、全体計画、すなわち総括班、および第I、II、III班の研究企画、計画内容につき、調整、並びに検討を加えた。具体的には、血管内皮細胞、血管平滑筋細胞、さらに血液細胞それぞれの形質変換と脱分化・分化を中心命題として研究を進め、さらに、血管構成細胞間の、あるいは血管構成細胞と血液細胞との細胞間の相互連関、それに関与する生物学的及び物理的刺激のシグナル伝達の分子機構を合わせ研究し、臓器としての血管の構築と動脈硬化の分子機構の解明を分子生物学、細胞生物学レベルで重点的に推進することとした。さらに、本研究に対し、本年度公募研究211題について、研究企画、計画内容、独創性、将来性を検討し、研究計画第I、II、III班、それぞれに必要な公募研究39題を採択した。この決定に基づき、平成9年度から4年間研究推進が実行に移されることになった。

研究成果

(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Tnaka,M.et al.: "Regulation of apolipoprotein B secretion in hepatocytes from Watanabe heritable hyperlipidemic rabbit,an animal model" Atherosclerosis. 114. 73-82 (1995)
[文献書誌] Ochi,H.et al.: "Elevated levels of cyclic AMP inhibits protein kinase-C independent mechanisms of endothelial PDGF-B chain and TCAM-1 gene induction by lysophosphatidylcholine." Circulation Research. 77. 530-535 (1995)
[文献書誌] Kita,T.et al.: "Lessons concerning human lipoprotein metabolism from the study of the WHHL rabbit." Atherosclerosis. x. 111-113 (1995)
[文献書誌] Uematsu,M.et al.: "Coexistent myelodysplastic syndrome and non-Hodgkin lymphoma. Report of a case and review of the literature." Int.J.Hematology. 62. 45-51 (1995)
[文献書誌] Kume,N.et al.: "Involvement of protein kinase C-independent mechanisms in endothelial ICAM-1 up-regulation by lysophosphatidylcholine." Ann.N.Y.Acad.Sci.748. 541-542 (1995)
[文献書誌] Komatsu,T.et al.: "Lipoprotein glomerulopathy with a new apolipoproteins E phenotype" Am.J.Kidney Diseases. 25. 952-953 (1995)
[文献書誌] Nishida,R.et al.: "Endoscopic Sclerotherapy in a Rat Model of Esophageal Varices" Scand J.Gastroenterol. 30. 489-496 (1995)
[文献書誌] Dekigai,H.et al.: "Mechanism of Helicobacter pylori-Associated Gastric Mucosal Injury" Digestive Diseases and Sciences. 40. 1332-1339 (1995)
[文献書誌] Teramoto,T.et al.: "Clinical Efficacy of luvastatin for hyperlipidemia in Japanese patients." Am.J.Cardiol.76. 33A-36A (1995)
[文献書誌] Yokode,M.et al.: "The macrophage and its role in atherogenesis" Internal Medicine. 34. 281-283 (1995)
[文献書誌] Yokode,M.et al.: "Cigarette smoke and lipoprotein modification : a possible interpretation for development of atherosclerosis." Ann.N.Y.Acad.Sci.748. 294-301 (1995)
[文献書誌] Iehara,N.et al.: "Differentiation of smooth muscle phenotypes in mouse mesangial cells." Kid.Int.49. 1330-1341 (1996)
[文献書誌] Iehara,N.et al.: "Advanced glycosylation endoproducts modulate transcriptional regulations of type IV collagen and α-smooth muscle action mesangial cells." Nephrology. 118. 141-146 (1996)
[文献書誌] Uematsu-Yanagita,M.et al.: "Microscopic polyarteritis during polymyalgia rheumatica remission." Am.J.Kid.Dis.28. 289-291 (1996)
[文献書誌] Yokode,M.et al.: "Modification of high-and low-density lipoproteins by cigarette smoke oxidants." The Ann.N.Y.Acad.Sci.786. 245-251 (1996)
[文献書誌] Kita,T.et al.: "Lysophosphatidylcholine induced gene expression of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1." Medical Science Symposia Series. (in press).
[文献書誌] Kita,T.et al.: "Induction of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1 by lysophosphatidylcholine" The Ann.N.Y.Acad.Sci.(in press).
[文献書誌] Sakai,A.et al.: "P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesteroleic rabbits prior to intimal accumulation of Macrophages and T-lymphocytes." Arterioscler Thromb Vasc Biol.(in press).
[文献書誌] Nishi,E.et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation Research. (in press).
[文献書誌] Sawamura,T.et al.: "A novel endothelial receptor for oxidized LDL" Nature. (in press).

1996 年度 実績報告書

動脈硬化の分子機構

研究代表者

北 徹 京都大学, 医学研究科, 教授 (60161460)

研究成果

[文献書誌] Tnaka,M.et al.: "Regulation of apolipoprotein B secretion in hepatocytes from Watanabe heritable hyperlipidemic rabbit,an animal model" Atherosclerosis. 114. 73-82 (1995)

[文献書誌] Ochi,H.et al.: "Elevated levels of cyclic AMP inhibits protein kinase-C independent mechanisms of endothelial PDGF-B chain and TCAM-1 gene induction by lysophosphatidylcholine." Circulation Research. 77. 530-535 (1995)

[文献書誌] Kita,T.et al.: "Lessons concerning human lipoprotein metabolism from the study of the WHHL rabbit." Atherosclerosis. x. 111-113 (1995)

[文献書誌] Uematsu,M.et al.: "Coexistent myelodysplastic syndrome and non-Hodgkin lymphoma. Report of a case and review of the literature." Int.J.Hematology. 62. 45-51 (1995)

[文献書誌] Kume,N.et al.: "Involvement of protein kinase C-independent mechanisms in endothelial ICAM-1 up-regulation by lysophosphatidylcholine." Ann.N.Y.Acad.Sci.748. 541-542 (1995)

[文献書誌] Komatsu,T.et al.: "Lipoprotein glomerulopathy with a new apolipoproteins E phenotype" Am.J.Kidney Diseases. 25. 952-953 (1995)

[文献書誌] Nishida,R.et al.: "Endoscopic Sclerotherapy in a Rat Model of Esophageal Varices" Scand J.Gastroenterol. 30. 489-496 (1995)

[文献書誌] Dekigai,H.et al.: "Mechanism of Helicobacter pylori-Associated Gastric Mucosal Injury" Digestive Diseases and Sciences. 40. 1332-1339 (1995)

[文献書誌] Teramoto,T.et al.: "Clinical Efficacy of luvastatin for hyperlipidemia in Japanese patients." Am.J.Cardiol.76. 33A-36A (1995)

[文献書誌] Yokode,M.et al.: "The macrophage and its role in atherogenesis" Internal Medicine. 34. 281-283 (1995)

[文献書誌] Yokode,M.et al.: "Cigarette smoke and lipoprotein modification : a possible interpretation for development of atherosclerosis." Ann.N.Y.Acad.Sci.748. 294-301 (1995)

[文献書誌] Iehara,N.et al.: "Differentiation of smooth muscle phenotypes in mouse mesangial cells." Kid.Int.49. 1330-1341 (1996)

[文献書誌] Iehara,N.et al.: "Advanced glycosylation endoproducts modulate transcriptional regulations of type IV collagen and α-smooth muscle action mesangial cells." Nephrology. 118. 141-146 (1996)

[文献書誌] Uematsu-Yanagita,M.et al.: "Microscopic polyarteritis during polymyalgia rheumatica remission." Am.J.Kid.Dis.28. 289-291 (1996)

[文献書誌] Yokode,M.et al.: "Modification of high-and low-density lipoproteins by cigarette smoke oxidants." The Ann.N.Y.Acad.Sci.786. 245-251 (1996)

[文献書誌] Kita,T.et al.: "Lysophosphatidylcholine induced gene expression of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1." Medical Science Symposia Series. (in press).

[文献書誌] Kita,T.et al.: "Induction of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1 by lysophosphatidylcholine" The Ann.N.Y.Acad.Sci.(in press).

[文献書誌] Sakai,A.et al.: "P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesteroleic rabbits prior to intimal accumulation of Macrophages and T-lymphocytes." Arterioscler Thromb Vasc Biol.(in press).

[文献書誌] Nishi,E.et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation Research. (in press).

[文献書誌] Sawamura,T.et al.: "A novel endothelial receptor for oxidized LDL" Nature. (in press).

1996 年度実績報告書

北徹京都大学, 医学研究科, 教授 (60161460)