The Development of Next-generation Therapeutics for Myocardial Infarction

下一代心肌梗塞治疗药物的开发

• 批准号: 21790755
• 负责人: NAKATA Sei
• 金额: $ 2.66万
• 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 Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790755/
• 关键词: 分子血管病態学; 一酸化窒素合成酵素; アンジオテンシンII; 心不全; 心肥大; 動脈硬化; 高脂血症; LDL受容体

A spontaneous myocardial infarction based on metabolic syndrome and coronary arteriosclerosis was observed in the triply NOS(-/-) mice that we have recently developed. Then, I hit on an idea using this mouse to research for the novel therapy of a myocardial infarction. Long-term treatment with olmesartan (angiotensin II type 1 receptor blocker) significantly improved all these metabolic phenotypes and coronary lesion formation in the triply NOS(-/-) mice. Long-term treatment with atorvastatin (HMG-CoA reductase inhibitor) also significantly alleviated all the metabolic phenotypes and coronary lesion formation in the triply NOS(-/-) mice. Furthermore, long-term treatment with isosorbide dinitrate (NO donor) significantly ameliorated all the metabolic phenotypes in the triply NOS(-/-) mice. These results indicate beneficial effect of these medicines for the metabolic syndrome and coronary lesion formation, which are causes of myocardial infarction, demonstrating important findings in therapeutic for myocardial infarction. The prevent effect for myocardial infarction by these medicines is expected, and is presently under study.

在我们最近开发的三重NOS(-/-)小鼠中观察到基于代谢综合征和冠状动脉硬化的自发性心肌梗死。然后，我想到了用这只老鼠来研究心肌梗塞的新疗法。奥美沙坦（血管紧张素 II 1 型受体阻滞剂）的长期治疗显着改善了三重 NOS(-/-) 小鼠的所有这些代谢表型和冠状动脉病变形成。阿托伐他汀（HMG-CoA还原酶抑制剂）的长期治疗也显着减轻了三重NOS（-/-）小鼠的所有代谢表型和冠状动脉病变形成。此外，长期使用硝酸异山梨酯（NO供体）治疗显着改善了三重NOS（-/-）小鼠的所有代谢表型。这些结果表明这些药物对代谢综合征和冠状动脉病变形成具有有益作用，而代谢综合征和冠状动脉病变形成是心肌梗塞的原因，这证明了心肌梗塞治疗中的重要发现。这些药物对心肌梗塞的预防作用值得期待，目前正在研究中。

项目成果

心筋梗塞の病因におけるNO合成酵素システムの役割

NO合酶系统在心肌梗死发病机制中的作用

• 发表时间: 2009
• 作者: 名越智古;吉村道博;松浦勝久;中田靖
• 通讯作者: 中田靖

Critical Role of Renin-Angiotensin Axis in Pathogenisis of Acute Myocardial Infarction in Mice Entire Nitric Oxide Synthase System

肾素-血管紧张素轴在小鼠急性心肌梗死发病机制中的关键作用全一氧化氮合酶系统

• 发表时间: 2009
• 作者: Kamiya K;Masuda T;Miida K;Matsunaga A;Ogura MN;Kimura M;Noda C;Yamaoka-Tojo M;Izumi T;Nakata S
• 通讯作者: Nakata S

Critical Role of Nitric Oxide Stnthase System in the Pathogenesis of Dyslipidemia : Lesson from Mice Lacking All Nitric Oxide Synthases

一氧化氮合酶系统在血脂异常发病机制中的关键作用：缺乏所有一氧化氮合酶的小鼠的教训

• 发表时间: 2010
• 作者: 名越智古;吉村道博;義久精臣;Yatera Y
• 通讯作者: Yatera Y

Severe Dyslipidemia, Atherosclerosis, and Sudden Cardiac Death in Mice Lacking A11 NO Synthases Fed a High-Fat Diet

高脂饮食缺乏 A11 NO 合成酶的小鼠出现严重血脂异常、动脉粥样硬化和心脏猝死

• 发表时间: 2010
• 期刊: Cardiovasc Res. (In press)
• 作者: Yatera Y,…;Nakata S(6番目)
• 通讯作者: Nakata S(6番目)