Development of new therapies and significance of adrenomedullin and mast cells in the abdominal aortic aneurysm.

腹主动脉瘤新疗法的开发以及肾上腺髓质素和肥大细胞的意义。

• 批准号: 22390161
• 负责人: KITAMURA Kazuo
• 金额: $ 11.4万
• 依托单位: University of Miyazaki
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390161/
• 关键词: アドレノメデュリン; 腹部大動脈瘤; マスト細胞; 血管作動性ペプチド; 炎症性サイトカイン; 血管外膜; 老化; 炎症; 外膜; マクロファージ; トラニラスト; サイトカイン; コラゲナーゼ

Abdominal aortic aneurysm (AAA) develops based on advanced atherosclerosis; however, the underlying pathogenesis remains unknown. Adrenomedullin (AM) is widely expressed in various organs and tissues, and has anti-inflammatory, anti-oxidant and angiogenic activity. We have reported that AM is produced in mast cells of human AAA and that AM exhibited the anti-fibrotic activity on fibroblasts. We investigated the role of AM in the development of AAA in 12 weeks-old male apoE-/- mice bred with AM heterozygous, or its role when recombinant human (rh)AM was administrated to the apoE-/- male mice, which was infused with 1000ng/kg/min of angiotensin II for 28 days. Mortality tended to be higher in rhAM at 3000ng/kg/hr. Both the incidence and the size of AAA were not significant between the groups. Because of dual nature of AM action on progression or protection of AAA, we may not have observed the biological actions of AM in the development of AAA.

腹主动脉瘤（AAA）发生于晚期动脉粥样硬化；然而，潜在的发病机制尚不清楚。肾上腺髓质素（AM）广泛表达于各种器官和组织中，具有抗炎、抗氧化和血管生成活性。我们已经报道了AM在人AAA肥大细胞中产生，并且AM对成纤维细胞表现出抗纤维化活性。我们研究了AM在12周龄的apoE-/-雄性杂合小鼠AAA发生中的作用，以及重组人（rh）AM给apoE-/-雄性小鼠，并给其注入1000ng/kg/min的血管紧张素II 28天后的作用。3000ng/kg/hr的rhAM死亡率更高。两组间AAA的发生率和大小均无显著性差异。由于AM对AAA进展或保护的双重作用，我们可能没有观察到AM在AAA发展中的生物学作用。

项目成果

Adrenomedullin : Roles for structure and function in cardiac or vascular tissues

肾上腺髓质素：在心脏或血管组织中的结构和功能的作用

• 发表时间: 2011
• 期刊: Current Hypertension Reviews
• 影响因子: 2.3
• 作者: Tsuruda T;Kitamura K
• 通讯作者: Kitamura K

Adrenomedullin does not contribute toward the development of abdominal aortic aneurysm in mice.

肾上腺髓质素不会促进小鼠腹主动脉瘤的形成。

• DOI: 10.4236/health.2014.610133
• 发表时间: 2014
• 期刊: Health
• 影响因子: 2.1
• 作者: Sakamoto S;Tsuruda T;Hatakeyama K;Shimosawa T;Asada Y;Kitamura K.
• 通讯作者: Kitamura K.

Inhibition of Development of Abdominal Aortic Aneurysm by Glycolysis Restriction

• DOI: 10.1161/atvbaha.111.237065
• 发表时间: 2012-06-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Tsuruda, Toshihiro;Hatakeyama, Kinta;Kitamura, Kazuo
• 通讯作者: Kitamura, Kazuo

Glucose metabolism in macrophages contributes to the development of atherosclerosis in apolipoprotein E knockout mice

巨噬细胞中的葡萄糖代谢有助于载脂蛋白 E 敲除小鼠动脉粥样硬化的发展

• 发表时间: 2013
• 作者: 郝異琳;鶴田敏博;関田陽子;坂元紀陽;畠山金太;浅田祐士郎;北村和雄
• 通讯作者: 北村和雄

Age dependent and regional difference of Inflammatory responses in the development of atherosclerosis in apolipoprotein E knockout mice

载脂蛋白E基因敲除小鼠动脉粥样硬化发展中炎症反应的年龄依赖性和区域差异

• 发表时间: 2011
• 作者: Sakamoto S;Tsuruda T;Kitamura K
• 通讯作者: Kitamura K