Research on the pathogenis and protection of Atherosclerosis

动脉粥样硬化发病机制及防治研究

• 批准号: 62570393
• 负责人: ONISHI Toshio
• 金额: $ 1.15万
• 依托单位: Osaka University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570393/
• 关键词: Vascular Smooth Muscle Cells; Proliferation; Glycosaminoglycan; Vitamin D; Intracellular Ca^<2+>; Ca^<2+>-ATPase; Low Density Lipoprotein; 血小板由来成長因子; 動脈硬化; 血管平滑筋細胞; プロスタグランディン; 細胞内カルシウム; 活性型ビタミンD; 血小板由来増殖因子; カルシウム拮抗剤

1. Research on the Pathogenesis of Atherosclerosis: Proliferation of vascular smooth muscle cells (VSMC) and deposition of lipid is important for the pathogenesis of atherosclerosis.1) Vascular smooth muscle cells from rat aorta contaied a specific receptor for the 1,25-dihydroxyvitamin D_3 and it stimulated the proliferation and suppressed the synthesis of glycosaminoglycan.2) Platelet derived growth factor (PDGF) increased intracellular Ca^<2+> concentration ([Ca^<2+>] i) in rabbit chondrocytes and stimulated the synthesis of DNA and glycosaminoglycan. Suramin, an antagonist of PDGF, suppressed the increase of [Ca^<2+>] i and the synthesis of DNA.3) Low density lipoprotein (LDL) increased [Ca^<2+>] i. LDL caused a release of Ca^<2+> from intracellular Ca^<2+> store through production of inositole trisphosphate (iP_3).4) A specific receptor for PDGF existed in the basolateral membrane of dog kidney and PDGF stimulated Ca^<2+>- ATPase.2. Reaserch for the effects of various chemical compounds on the intracellular Ca^<2+> signal system.1) Prostaglandin F2 and angiotensin II (AII), both of which are strong vasoconstrictor, increased [Ca^<2+>] i in VSMC and caused the release of Ca^<2+> from intracellular Ca^<2+> store. Nicorandil, a vasodilator, suppressed the increase of [Ca^<2+>] i induced by prostaglandin F2 and AII.2) Valinomycin, a potassium ionophore, suppressed the release of CA^<2+> from intracellular Ca^<2+> store induced by AII but did not suppress those induced by ionomycin, a Ca^<2+> ionophore. However valinomycin did not sauppress the production of iP_3 induced by AII.3) Nitroglycerin and nicorandil, which are nitrates, stimulated the activities of Ca^<2+>-ATPase in the microsmal fraction of porcine coronary artery smooth muscle cells, but Ca^<2+> channel blockers did not.

1.动脉粥样硬化的发病机制研究：血管平滑肌细胞（VSMC）的增殖和脂质沉积在动脉粥样硬化的发病机制中起重要作用。1）大鼠主动脉血管平滑肌细胞含有1，25-二羟维生素D_3刺激细胞增殖，抑制糖胺聚糖的合成; 2）血小板源性生长因子（PDGF）增加细胞内Ca ~（2+）>浓度（[Ca^<2+>] i），并刺激DNA和糖胺聚糖的合成。PDGF拮抗剂苏拉明可抑制[Ca^<2+>] i的升高和DNA的合成; 3）低密度脂蛋白（LDL）可升高[Ca^<2+>] i。LDL通过产生三磷酸肌醇（iP_3）引起细胞内Ca^<2+>库中Ca^<2 +>的释放。4）狗肾基底外侧膜上存在一种PDGF的特异性受体，并且PDGF刺激Ca^<2+>-ATP酶。2. 1）前列腺素F2和血管紧张素II（Angiotensin II，AII）均为强缩血管剂，可使VSMC [Ca^2+] i增加，引起细胞内Ca^2+库释放Ca^2+。2）钾离子载体缬氨霉素抑制AII诱导的细胞内Ca ^2+库释放Ca ^2+，但不抑制钙离子载体离子霉素诱导的细胞内Ca^2+库释放Ca^2+。3）硝酸甘油和尼可地尔对猪冠状动脉平滑肌细胞的Ca^<2+>-ATP酶活性有促进作用，而Ca^<2 +>通道阻断剂则无此作用。

项目成果

Koh Eio.: Life Sciences. 42. 215-223 (1988)

Koh Eio.：生命科学。

Fukuo, Keisuke: "Effects of prostaglandins on the cytosolic free calcium concentration in vascular smooth muscle cells." Biochem. Biophys. Res. Commun.136. 247-252 (1986)

Fukuo，Keisuke：“前列腺素对血管平滑肌细胞胞质游离钙浓度的影响。”

Fukuo, Keisuke.: "Inhibitory effects of suramin on inductions by platelet-derived growth factor of mitogenesis and increase in cytosolic Ca^<2+> in chondrocytes." Cell Calcium. in press. (1989)

Fukuo, Keisuke.：“苏拉明对血小板衍生生长因子诱导有丝分裂和软骨细胞中胞质 Ca^2 增加的抑制作用。”

Morita Ryuhei.: "Low density lipoprotein and apoprotein B induce increase in inositol trisphosphate and cytosolic free Ca^<2+> in vascular smooth muscle cells." Biochemistry International. 18. 647-653 (1989)

Morita Ryuhei.：“低密度脂蛋白和脱辅基蛋白 B 诱导血管平滑肌细胞中肌醇三磷酸和胞质游离 Ca^2 的增加。”

Koh, Eio: "Effects of nitrates and calcium channel blockers on Ca^<2+>-ATPase in the Mecrosomal fraction of porcine coronary artery smooth muscle cells." Cell Calcium.8. 397-410 (1987)

Koh，Eio：“硝酸盐和钙通道阻滞剂对猪冠状动脉平滑肌细胞巨大体部分中Ca 2+ -ATP酶的影响。”