Evaluation of new nanotechnology to raise HDL cholesterol level and elucidation of its molecular mechanism

新型纳米技术提高HDL胆固醇水平的评价及其分子机制的阐明

• 批准号: 23659463
• 负责人: SHIMANO Hitoshi
• 金额: $ 2.5万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659463/
• 关键词: リポタンパク質; 動脈硬化; 胆汁酸; ナノテクノロジー; 脂質異常症

Raising HDL-cholesterol (C) has emerged as a potential strategy to tackle the residual risk that remains even after lowering LDL-C and triglyceride, in preventing cardiovascular disease. PEGylated and quaternized polyamine nanogel (Q-Nanogel) is a newly synthesized bile salt sequestering agent intended to treat dyslipidemia. We assessed the effects of Nanogel on dyslipidemia and atherosclerosis. Nanogel treatment resulted in a 35% reduction in plasma VLDL/LDL-C levels, a 58% increase in plasma HDL-C levels in C57BL/6J mice. In LDLR-/-mice, atherosclerotic lesion size with Nanogel was reduced by 45% compared to PBS. These data indicate that Nanogel not only decreased VLDL/LDL-C levels but also raised HDL-C levels. Nanogel could be a potential therapeutic candidate to raise HDL-C and the treatment of atherosclerosis.

提高高密度脂蛋白胆固醇(C)已成为一种潜在的策略，以解决即使在降低低密度脂蛋白胆固醇和甘油三酯后仍然存在的残留风险，以预防心血管疾病。聚乙二醇化和季铵化多胺纳米凝胶（Q-Nanogel）是一种新合成的胆汁盐隔离剂，用于治疗血脂异常。我们评估了纳米凝胶对血脂异常和动脉粥样硬化的影响。纳米凝胶治疗导致C57BL/6J小鼠血浆VLDL/LDL-C水平降低35%，血浆HDL-C水平升高58%。在LDLR-/-小鼠中，与PBS相比，Nanogel减少了45%的动脉粥样硬化病变。这些数据表明，纳米凝胶不仅降低了VLDL/LDL-C水平，而且提高了HDL-C水平。纳米凝胶可能是提高HDL-C和治疗动脉粥样硬化的潜在候选药物。

项目成果

Sterol Regulatory Element-Binding Protein-1 Determines Plasma Remnant Lipoproteins and Accelerates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

• DOI: 10.1161/atvbaha.110.219659
• 发表时间: 2011-08-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Karasawa, Tadayoshi;Takahashi, Akimitsu;Shimano, Hitoshi
• 通讯作者: Shimano, Hitoshi

Macrophage Elovl6 Deficiency Ameliorates Foam Cell Formation and Reduces Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

• DOI: 10.1161/atvbaha.110.221663
• 发表时间: 2011-09-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Saito, Ryo;Matsuzaka, Takashi;Shimano, Hitoshi
• 通讯作者: Shimano, Hitoshi

動脈硬化戦略における脂質管理の新しい視点:臓器脂質の量的制御と質的制御

动脉粥样硬化策略中脂质管理的新视角：器官脂质的定量和定性控制

• 发表时间: 2011
• 作者: Hirotaka Matsuo;Tappei Takad;Kimiyoshi Ichida;et al.;清水文崇;島野仁
• 通讯作者: 島野仁

Macrophage Elovl6 deficiency ameliorates foam cell formation and reduces atherosclerosis in low-density liporotein receptor-deficient mice

巨噬细胞Elovl6缺陷改善低密度脂蛋白受体缺陷小鼠泡沫细胞形成并减少动脉粥样硬化

• 发表时间: 2011
• 期刊: Arterioscle Thromb Vasc Biol
• 作者: Saito R;Matsuzaka T;Yamada N;Shimano H;et al
• 通讯作者: et al

Novel qualitative aspects of tissue fatty acids related to metabolic regulation : Lessons from Elvol6 knockout

与代谢调节相关的组织脂肪酸的新定性方面：Elvol6 敲除的教训

• 发表时间: 2012
• 期刊: Prog Lipid Res
• 影响因子: 13.6
• 作者: Sato-Horiguchi C;Ogawa D;Wada J;Tachibana H;Kodera R;Eguchi J;Nakatsuka A;Terami N;Shikata K;Makino H.;小島博;吉良潤一;窪田直人;Shimano H
• 通讯作者: Shimano H