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通过内皮素以外的其他血管活性多肽参与肺动脉高压和肺纤维化发病机制的可能性。我们通过上调缓激肽系统，证明了ECEs杂合子小鼠对低氧所致的肺动脉高压具有抵抗作用。通过增强CGRP途径，我们还发现了ECEs杂合子小鼠对博莱霉素诱导的肺纤维化具有抵抗力。这些结果表明，ECEs在肺高压和肺纤维化的发病机制中起着重要作用，并可能成为治疗这些疾病的靶点。

项目成果

A new class of drug for pulmonary arterial hypertension. Can a Rho-kinase inhibitor break the stagnation in treating it?

一类新的肺动脉高压药物。

• DOI: 10.1253/circj.cj-13-0951
• 发表时间: 2013
• 期刊: Circulation journal : official journal of the Japanese Circulation Society
• 作者: K. Miyagawa;N. Emoto
• 通讯作者: N. Emoto

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.

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

Role of Bradykinin and Endothelin-Converting Enzyme-1 in Pulmonary Hypertension

缓激肽和内皮素转换酶 1 在肺动脉高压中的作用

• 发表时间: 2013
• 作者: Raharjo SB;Emoto N;Yuniadi Y;Nakayama K;Harimurti GM
• 通讯作者: Harimurti GM