Functional analysis of Angiotensin Receptor Binding Protein in The Cardiovascular Regulation

血管紧张素受体结合蛋白在心血管调节中的功能分析

• 批准号: 20590979
• 负责人: TAMURA Kouichi
• 金额: $ 3万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590979/
• 关键词: 高血圧学; 分子心臓血管病態学; シグナル伝達; 循環器・高血圧; 生体分子; 生理活性; トランスレーショナルリサーチ

We hypothesized that a downregulation of the cardiac ATRAP to angiotensin II type 1 receptor ratio is involved in the pathogenesis of cardiac hypertrophy. To examine this hypothesis, we next generated transgenic mice expressing ATRAP specifically in cardiomyocytes under control of the α-myosin heavy chain promoter. In cardiac-specific ATRAP transgenic mice, the development of cardiac hypertrophy, activation of p38 mitogen-activated protein kinase, and expression of hypertrophy-related genes in the context of angiotensin II treatment were completely suppressed, in spite of there being no significant difference in blood pressure on radiotelemetry between the transgenic mice and littermate control mice. These results demonstrate that cardiomyocyte-specific overexpression of ATRAP in vivo abolishes the cardiac hypertrophy provoked by chronic angiotensin II infusion, thereby suggesting ATRAP to be a novel therapeutic target in cardiac hypertrophy.

我们推测心脏ATRAP与血管紧张素II 1型受体比例的下调参与了心脏肥大的发病机制。为了验证这一假设，我们接下来产生了在α-肌球蛋白重链启动子控制下的心肌细胞中特异性表达ATRAP的转基因小鼠。在心脏特异性ATRAP转基因小鼠中，血管紧张素II治疗背景下心脏肥大的发生、p38有丝分裂原活化蛋白激酶的激活以及肥大相关基因的表达均被完全抑制，尽管转基因小鼠和同窝对照小鼠之间的无线电遥测血压没有显着差异。这些结果表明，心肌细胞特异性过表达ATRAP在体内废除慢性血管紧张素II输注引起的心脏肥大，从而表明ATRAP是一种新的治疗靶点在心脏肥大。

项目成果

Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant -: Implications for essential hypertension

• DOI: 10.1161/hypertensionaha.107.102061
• 发表时间: 2008-03-01
• 期刊: HYPERTENSION
• 影响因子: 8.3
• 作者: Araki, Naomi;Umemura, Masanari;Ishigami, Tomoaki
• 通讯作者: Ishigami, Tomoaki

AT1受容体阻害薬は高血圧合併腹膜透析患者の血圧短期変動性を改善する.シンポジウム4:透析患者の心血管事故に及ぼす神経・内分泌因子の影響

AT1受体抑制剂改善腹膜透析高血压患者的短期血压变异性。研讨会4：神经内分泌因素对透析患者心血管意外的影响

• 发表时间: 2009
• 作者: 田村功一;他
• 通讯作者: 他

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Effect of olmesartan on tissue expression balance between angiotensin II receptor and its inhibitory binding molecule

• DOI: 10.1161/hypertensionaha.108.117341
• 发表时间: 2008-10-01
• 期刊: HYPERTENSION
• 影响因子: 8.3
• 作者: Shigenaga, Atsu-ichiro;Tamura, Kouichi;Umemura, Satoshi
• 通讯作者: Umemura, Satoshi

Effects of Angiotensin II Type 1 Receptor Blocker on Blood Pressure Variability and Cardiovascular Remodeling in Hypertensive Patients on Chronic Peritoneal Dialysis

• DOI: 10.1159/000210572
• 发表时间: 2009-01-01
• 期刊: NEPHRON CLINICAL PRACTICE
• 作者: Shigenaga, Atsu-ichiro;Tamura, Kouichi;Umemura, Satoshi
• 通讯作者: Umemura, Satoshi