EFFECTS OF EXAGGERATED BLOOD PRESSURE VARIABILITY ON CARDIAC REMODELING AND PERIVASCULAR INFLAMMATION

夸大的血压变异性对心脏重构和血管周围炎症的影响

• 批准号: 15590780
• 负责人: KAI Hisashi
• 金额: $ 2.24万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590780/
• 关键词: blood pressure variability; myocardial fibrosis; hypertension; hypertrophy; macrophages; アンジオテンシンII; 拡張障害; リモデリング; 接着因子; アンジオテニシンII; 拡張能障害

(1)To clarify the mechanism whereby wide blood pressure variability induces exaggerated hypertensive organ damages, we created new animal model of hypertension with large blood pressure variability by performing bilateral sino-aortic denervation(SAD) in spontaneously hypertensive rats(SHRs).(2)In SHR+SAD, mean blood pressure elevated to the similar level to that in SHR+sham operation. However, parameters of blood pressure variability, such as standard deviation of mean blood pressure and coefficent of variation of mean blood pressure, were significantly larger in SHR+SAD than in SHR+sham operation.(3)SHR+SAD had enhanced left ventricular hypertrophy and severer myocardial fibrosis, compared with SHR+sham operetion.(4)SAD remarkably upregulated myocardial MCP-1 expression and enhanced perivascular macrophage infiltration in the hearts of SHR.

(1)To为了阐明大范围血压变异性导致高血压器官损害的机制，我们通过对自发性高血压大鼠（SHR）进行双侧去窦主动脉神经（SAD）建立了一种新的大范围血压变异性高血压动物模型。(2)In SHR+SAD组平均血压升高至与SHR+假手术组相似水平。而SHR+SAD组血压变异性参数（平均血压标准差和平均血压变异系数）明显大于SHR+假手术组。（3）SHR+SAD组左室肥厚和心肌纤维化程度较SHR+Sham组明显加重。（4）SAD可显著上调SHR心肌MCP-1表达，增加心肌血管周围巨噬细胞浸润。

项目成果

Inhibition of STAT3 prevents neointime formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells.

抑制 STAT3 通过抑制新生内膜平滑肌细胞的增殖和促进其凋亡来防止新生内膜形成。

• 发表时间: 2003
• 期刊: Human Gene Ther 14(7)
• 作者: Shibata R;Kai H;Seki Y;Kato S;Wada Y;Hanakawa Y;Hashimoto K;Yoshimura A;Imaizumi T.
• 通讯作者: Imaizumi T.

Sub-depressor dose of angiotensin type-1 receptor blocker inhibits TGF-β-mediated perivascular fibrosis in hypertensive rat hearts.

亚抑制剂剂量的血管紧张素 1 型受体阻滞剂可抑制高血压大鼠心脏中 TGF-β 介导的血管周围纤维化。

• 发表时间: 2003
• 期刊: J Cardiovasc Pharmacol 42(suppl)
• 作者: Tokuda K;Kai H;Kuwahara F;Imaizumi T
• 通讯作者: Imaizumi T

Pressure-Independent Effects of Angiotensin II on Hypertensive Myocardial Fibrosis

• DOI: 10.1161/01.hyp.0000111831.50834.93
• 发表时间: 2004-02
• 期刊: Hypertension: Journal of the American Heart Association
• 作者: K. Tokuda;H. Kai;F. Kuwahara;H. Yasukawa;N. Tahara;Hiroshi Kudo;Kiyoko Takemiya;M. Koga;Tomoka Yamamoto;T. Imaizumi

Hypertensive myocardial fibrosis and Diastolic dysfunction - Another model of inflammation?

• DOI: 10.1161/01.hyp.0000118584.33350.7d
• 发表时间: 2004-04-01
• 期刊: HYPERTENSION
• 影响因子: 8.3
• 作者: Kuwahara, F;Kai, H;Imaizumi, T
• 通讯作者: Imaizumi, T

Tokuda K, Kai H(他2名, 2番目): "Sub-depressor dose of angiotensin type-1 receptor blocker inhibits TGF-beta-mediated perivascular fibrosis in hypertensive rat hearts"J Cardiovasc Pharmacol. 42(suppl.1). S61-S65 (2003)

Tokuda K、Kai H（其他 2 名，第 2 名）：“亚抑制剂剂量的 1 型血管紧张素受体阻滞剂抑制高血压大鼠心脏中 TGF-β 介导的血管周围纤维化”J Cardiovasc Pharmacol 42（增刊 1）。 S65 (2003)