Effects of LDL on SMC Proliferation and Intracellular Signalings

LDL 对 SMC 增殖和细胞内信号转导的影响

• 批准号: 04454274
• 负责人: NAKASHIMA Yasuhide
• 金额: $ 2.82万
• 依托单位: University of Occupational and Environmental Health, Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454274/
• 关键词: Low-density lipoprotein; arterial smooth muscle cell; Intracellular Ca^<2+>; free cholesterol; フリーコレステロール; 動脈硬化退縮; プロブコール; ヂルチアゼム; イノシトール三リン酸; LDL; SMC; Ca^<++>

To elucidate the mechanism of low-density lipoprotein (LDL) from familial hypercholesterolemic (FH) human subjects on the cultured smooth muscle cell (SMC), cell proliferation, Ca2+ movements and membrane structure were examined, along with the antiproliferative action of heparin or sulfated glycosaminoglycans. Cell growth as well as Ca^<2+> uptake was stimulated in a concentration-dependent fashion with FH-LDL compared to control (without LDL). With methylated LDL, which had no capacity to bind LDL receptor, the proliferation and Ca2+ uptake were still significantly increased compared to control. But the about 60% of increase over control was reduced by methylation. In analysis of lipid composition, the exposure to FH-LDL elevated free cholesterol contents in SMC membrane. In structural analysis, FH-LDL brought the swelling in the intrabilayr and interbilayr structure compared to control, which well correlated with change in the increase in free cholesterol in plasma membrane. Heparin or sulfated glycosaminoglycans inhibited the cell proliferation with reduction of free cholesterol in plasma membrane. We concluded that FH-LDL might increase the free cholesterol composition in plasma membrane through LDL receptor-independent pathway, and that change structure of membrane, which affect Ca2+ channel function.

为了阐明家族性高胆固醇血症（FH）患者低密度脂蛋白（LDL）对培养的平滑肌细胞（SMC）增殖、Ca ~（2+）运动和膜结构的影响，沿着肝素或硫酸化糖胺聚糖的抗增殖作用。与对照组（无LDL）相比，FH-LDL以浓度依赖性方式刺激细胞生长和Ca^2+摄取。与甲基化的LDL，它没有能力结合LDL受体，增殖和Ca 2+摄取仍显着增加相比，对照组。但甲基化降低了约60%的增加。在脂质成分分析中，暴露于FH-LDL使SMC膜中游离胆固醇含量升高。在结构分析中，与对照相比，FH-LDL引起了双层内和双层间结构的肿胀，这与质膜中游离胆固醇增加的变化密切相关。肝素或硫酸化糖胺聚糖抑制细胞增殖，降低细胞膜游离胆固醇。结论：FH-LDL可能通过LDL受体非依赖性途径增加细胞膜游离胆固醇的含量，改变细胞膜结构，从而影响Ca ~（2+）通道功能。

项目成果

H.Tasaki、K.Yamashita、Y.Nakashima、et al: "LDL from Familial Hypercholesterolemic Subjects Promotes Arterial Smooth Muscle Cell Proliferation" Journal of Japan Atherosclerosis Society. (In press).

H. Tasaki、K. Yamashita、Y. Nakashima 等人：“家族性高胆固醇血症受试者的低密度脂蛋白促进动脉平滑肌细胞增殖”，日本动脉粥样硬化学会杂志（正在出版）。

H.Tasaki、K.Yamashita、Y.Nakashima、et al: "Increase of Intracellular Calcium Ion in Smooth Muscle Cell Induced by Low-Density Lipoprotein" Gerontrogy. (In press).

H. Tasaki、K. Yamashita、Y. Nakashima 等人：“低密度脂蛋白诱导的平滑肌细胞内钙离子增加”老年学（正在出版）。

R.Kouzuma,H.Tasaki Y.Nakashima,et al: "Combined Treatment of Probucol with Dilfiazem Regresses Althrosclerosis Induced by 1%Cholesterol-diet in Rabbit Aorta." Arteriosclerosis and Thrombosis. Submitting.

R.Kouzuma,H.Tasaki%20Y.Nakashima,et%20al:%20"联合%20治疗%20of%20普罗布考%20与%20地尔花%20回归%20关节硬化%20诱导%20by%201%胆固醇饮食%20in%20兔%20主动脉

R.Kouzuma、H.Tasaki、Y.Nakashima、et al: "Combined Treatment of Probucol with Diltiazem Regresses Althrosclerosis Induced by 1% Cholesterol-diet in Rabbit Aorta" Arteriosclerosis and Thrombosis. (Submitting).

R. Kouzuma、H. Tasaki、Y. Nakashima 等人：“普罗布考与地尔硫卓联合治疗可逆转 1% 胆固醇饮食引起的兔主动脉动脉硬化”（提交）。

H.Tasaki, K.Yamashita, Y.Nakashima, et al: "LDL from Familial Hypercholesterolemic Subjects Promotes Arterial Smooth Muscle Cell Proliferation" Journal of Japan Atherosclerosis Society. (In press).

H.Tasaki、K.Yamashita、Y.Nakashima 等人：“来自家族性高胆固醇血症受试者的低密度脂蛋白促进动脉平滑肌细胞增殖”日本动脉粥样硬化学会杂志。