1993 Fiscal Year Annual Research Report

血管機能における神経・体液性因子の相関・病態

Research Project

Project/Area Number	04263104
Research Institution	Kyoto University
Principal Investigator	北徹京都大学, 医学部, 教授 (60161460)
Co-Investigator(Kenkyū-buntansha)	山本章国立循環器病センター, 研究所, 副所長 (00028408) 猿田享男慶応義塾大学, 医学部, 教授 (70051571) 泰江弘文熊本大学, 医学部, 教授 (40174502) 高井義美神戸大学, 医学部, 教授 (60093514) 河合忠一京都大学, 医学部, 名誉教授 (70025659)
Keywords	CNP / エンドセリン / NO / アクチビンA / PD-ECGF / Rho / 胎児型ミオシン重鎖 / リゾフォスファチジルコリン
Research Abstract	血管機能および神経並びに体液性因子の影響を血管内皮平滑筋に焦点をあてつつ、その分子機構を研究し病態生理的意義を明らかにすることを目的とする本班の第三年度の活動は順調に進展している。 (1)中尾らはCNPが内皮細胞において生成され、それがTGF-β、bFGFなど増殖因子およびIL-1α、βなどのサイトカインにより刺激されれることを明らかにした。広瀬らはANP受容体のホモダイマー構造を証明し、更にその遺伝子の転写制御機構の解析を進めている。 (2)エンドセリンに関しては越智らにより生体内分布が解析され、神経活性物質的及び成長因子的役割が明らかにされた。また熊田らは血管運動および呼吸に関わる神経伝達にエンドセリン-1の関与を見い出した。また広瀬、中尾らによりエンドセリン受容体遺伝子の転写調節機構の解析が進められている。 (3)猿田らはEDRFの本態であるNOが中枢神経系を介して交感神経活動を抑制している可能性を示唆し、平田らはDOCA-食塩高血圧ラットの病態がNO遊離減少に基づくことを明らかにした。竹下らは冠動脈のトーヌスとNOの関わりについて検討し、河合らはNO合成酵素の遺伝子の構造に基づきその発現調節の解析を進めている。加藤らはアストロサイトの内皮細胞への作用を解析している。 (4)小島らは平滑筋増殖制御をアクチビンAとの関わりにおいて解析し、豊島らはPD-ECGFの効果を酵素学的側面から明らかにしつつある。高井は血管平滑筋の移動にRhoの重要性を見い出した。また永井らは内膜における平滑筋細胞に胎児型ミオシン重鎖遺伝子の発現を明らかにするとともに、そのプロモーター領域の解析を進めつつある。 (5)リポ蛋白と血管構成細胞との関連においては、北らは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VCAM-1の発現をPKCを関与しない機構で誘導することを明らかにした。山本らはリポ蛋白リパーゼ(LPL)のマクロファージにおける生成とその病的意義を解析しつつある。また泰江らは冠動脈の攣縮とLPCの関わりにつき、一方友池らは遺伝的粥状動脈硬化モデルウサギを用いた内皮依存性弛緩反応の解析を行っている。

Research Products

(19 results)

All Other

All Publications (19 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 Kupffer 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] Itakura,M.,et al.: "Mutational analysis of disulfide bridges in the type C atrial natriuretic peptide receptor." J.Biol.Chem.in press.
[Publications] Iwashina,M.,et al.: "His^<145>-Trp146 residues and the disulfide-linked loops in atrial natriuretic peptide receptor are critial for the ligand-binding activity." J.Biochem.in press.
[Publications] Saruta,T.,et al.: "Efficacy of manidipine in the treatment of hypertension with renal impairment:Amulticenter trial." American Heart Journal. 125. 630-634 (1993)
[Publications] Kumagai,H.,et al.: "Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits." Circulation Research. 72. 1225-1265 (1993)
[Publications] Kugiyama,K.,et al.: "Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells." Circulation Research. 73. 335-343 (1993)
[Publications] Ohgushi,M.,et al.: "Protein kinase C inhibitors prevent impairment of endothelium-dependent relaxation by oxidatively modified LDL." Arteriosclerosis and Thrombosis. 13. 1525-1532 (1993)
[Publications] Uchizumi,H.,et al.: "A stable relaxing factor released from cytotoxic activated macrophages." Am.J.Physiol.264. H1472-H1477 (1993)
[Publications] Hattori,R.,et al.: "Stabilization of inducible nitric oxide synthase by monoclonal antibodies." Hybridoma. 12. 763-770 (1993)
[Publications] Hirata,Y.,et al.: "Role of endogenous ANP in DOCA-salt hypertensive rats:effects of a novel non-peptide antagonist for ANP receptor." Circulation. 87. 554-561 (1993)
[Publications] Hayakawa,H.,et al.: "Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats." Am.J.Physiol.264. H1535-H1541 (1993)
[Publications] Kigawa,K.,et al.: "Low-density lipoprotein receptor mutation that deletes exon 2 and 3 by Alu-Alu recombination." J.Biochem.113. 372-376 (1993)
[Publications] Takaichi,T.,et.al.: "Ultrastructural studies on the phenotypic modulation of human intimal smooth muscle cells." Atherosclerosis. 100. 197-211 (1993)
[Publications] Sasaki,T.,et al.: "Consequences of weak interaction of rho p21 and rac p21." J.Biol.Chem.268. 23959-23963 (1993)
[Publications] Kishi,K.,et al.: "Regulation of cytoplasmic division of Xenopus embyo by rho p21 and its inhibitory GDP/GTP exchange protein(rho GDI)." J.Cell.Biol.120. 1187-1195 (1993)
[Publications] Suga,S.,et al.: "Cytokine-induced C-type natriuretic peptide(CNP)secretion from vascular endothelial cells--Evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells--." Endocrinology. (in press).
[Publications] Arai,H.,et al.: "The human endothelin-B receptor gene--Structural organization and chromosomal addignment--." J.Biol.Chem.268. 3463-3470 (1993)

1993 Fiscal Year Annual Research Report

血管機能における神経・体液性因子の相関・病態

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 Kupffer 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] Itakura,M.,et al.: "Mutational analysis of disulfide bridges in the type C atrial natriuretic peptide receptor." J.Biol.Chem.in press.

[Publications] Iwashina,M.,et al.: "His^<145>-Trp146 residues and the disulfide-linked loops in atrial natriuretic peptide receptor are critial for the ligand-binding activity." J.Biochem.in press.

[Publications] Saruta,T.,et al.: "Efficacy of manidipine in the treatment of hypertension with renal impairment:Amulticenter trial." American Heart Journal. 125. 630-634 (1993)

[Publications] Kumagai,H.,et al.: "Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits." Circulation Research. 72. 1225-1265 (1993)

[Publications] Kugiyama,K.,et al.: "Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells." Circulation Research. 73. 335-343 (1993)

[Publications] Ohgushi,M.,et al.: "Protein kinase C inhibitors prevent impairment of endothelium-dependent relaxation by oxidatively modified LDL." Arteriosclerosis and Thrombosis. 13. 1525-1532 (1993)

[Publications] Uchizumi,H.,et al.: "A stable relaxing factor released from cytotoxic activated macrophages." Am.J.Physiol.264. H1472-H1477 (1993)

[Publications] Hattori,R.,et al.: "Stabilization of inducible nitric oxide synthase by monoclonal antibodies." Hybridoma. 12. 763-770 (1993)

[Publications] Hirata,Y.,et al.: "Role of endogenous ANP in DOCA-salt hypertensive rats:effects of a novel non-peptide antagonist for ANP receptor." Circulation. 87. 554-561 (1993)

[Publications] Hayakawa,H.,et al.: "Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats." Am.J.Physiol.264. H1535-H1541 (1993)

[Publications] Kigawa,K.,et al.: "Low-density lipoprotein receptor mutation that deletes exon 2 and 3 by Alu-Alu recombination." J.Biochem.113. 372-376 (1993)

[Publications] Takaichi,T.,et.al.: "Ultrastructural studies on the phenotypic modulation of human intimal smooth muscle cells." Atherosclerosis. 100. 197-211 (1993)

[Publications] Sasaki,T.,et al.: "Consequences of weak interaction of rho p21 and rac p21." J.Biol.Chem.268. 23959-23963 (1993)

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

[Publications] Suga,S.,et al.: "Cytokine-induced C-type natriuretic peptide(CNP)secretion from vascular endothelial cells--Evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells--." Endocrinology. (in press).

[Publications] Arai,H.,et al.: "The human endothelin-B receptor gene--Structural organization and chromosomal addignment--." J.Biol.Chem.268. 3463-3470 (1993)

北徹京都大学, 医学部, 教授 (60161460)