Investigation on vasopeptidase inhibition and its application to pulmonary hypertension

血管肽酶抑制及其在肺动脉高压中的应用研究

• 批准号: 23590123
• 负责人: EMOTO Noriaki
• 金额: $ 3.41万
• 依托单位: Kobe Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590123/
• 关键词: エンドセリン; エンドセリン変換酵素; ブラジキニン; 肺高血圧症; 肺線維症; 遺伝子欠損マウス; ブラジキニンニン; ナトリウム利尿ペプチド

We have investigated the possibilities that endothelin-converting enzyme (ECE) is involved in the pathogenesis of pulmonary hypertension and pulmonary fibrosis through other vasoactive peptides in addition to endothelin by using genetically modified mice. We have demonstrated that ECE heterozygous mice were resistant to develop hypoxia-induce pulmonary hypertension by upregulating bradykinin system. We also showed that ECE heterozygous mice were resistant to induce bleomycin-induced pulmonary fibrosis by potentiating CGRP pathway. These results suggest that ECE plays an important role to the pathogenesis of pulmonary hypertension and pulmonary fibrosis, and that ECE may be a plausible target for the therapeutic intervention to these disorders.

我们利用转基因小鼠研究了内皮素转换酶（ECE）通过除内皮素外的其他血管活性肽参与肺动脉高压和肺纤维化发病机制的可能性。我们已经证明，ECE 杂合子小鼠通过上调缓激肽系统来抵抗缺氧诱导的肺动脉高压。我们还表明，ECE 杂合子小鼠通过增强 CGRP 途径对诱导博来霉素诱导的肺纤维化具有抵抗力。这些结果表明，ECE 在肺动脉高压和肺纤维化的发病机制中发挥着重要作用，并且 ECE 可能是治疗干预这些疾病的合理目标。

项目成果

Endothelial cell-derived Endothelin-1 Knock-out Preserves Cortex Architecture after Ischemic-reperfusion Episode in Mice

内皮细胞源性内皮素 1 敲除可在小鼠缺血再灌注后保留皮质结构

• 发表时间: 2012
• 作者: Arfian N;Yagi K;Nakayama K;Ali H;Mayasari DS;Purnomo E;Emoto N
• 通讯作者: Emoto N

Fulton's Index was Considerably Higher in Endothelin-1 Transgenic Mice Compared to Their Littermates in Hypoxic Induced Pulmonary Arterial Hypertension but not Significantly between Gender

在缺氧引起的肺动脉高压中，内皮素 1 转基因小鼠的富尔顿指数显着高于其同窝小鼠，但性别间差异不显着

• 发表时间: 2014
• 作者: Satwiko MG;Nakayama K;Yagi K;Miyagawa K;Suzuki Y;Muliawan HS;Hirata KI;Emoto N
• 通讯作者: Emoto N

Endothelin Receptor Antagonist and Heart Failure

内皮素受体拮抗剂与心力衰竭

• 发表时间: 2014
• 作者: Jenkinson;S. F.;Thompson;A. L.;Nakagawa;S.;Kato;A.;Butters;T. D.;Fleet;G. W. J.;浜田奈々子，伊東秀記，田畑秀典，永田浩一;Emoto N.
• 通讯作者: Emoto N.

Vascular endothelium derived endothelin-1 is required for normal heart function after chronic pressure overload in mice.

• DOI: 10.1371/journal.pone.0088730
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Heiden S;Vignon-Zellweger N;Masuda S;Yagi K;Nakayama K;Yanagisawa M;Emoto N
• 通讯作者: Emoto N

ET-1 from endothelial cells is required for complete angiotensin II-induced cardiac fibrosis and hypertrophy

• DOI: 10.1016/j.lfs.2012.02.006
• 发表时间: 2012-10-15
• 期刊: LIFE SCIENCES
• 影响因子: 6.1
• 作者: Adiarto, Suko;Heiden, Susi;Emoto, Noriaki
• 通讯作者: Emoto, Noriaki