Thrombin receptor antagonists as a novel therapeutic agent for pulmonary hypertension

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10965
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kyushu University
• Principal Investigator: Maki Jun 九州大学, 大学病院, 助教 (10368665)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肺高血圧症 / 先天性心疾患 / トロンビン / トロンビン受容体

Outline of Final Research Achievements

I examined the usefulness of the Aorto-caval shunt in either rats and mice as an experimental model for our research of pulmonary hypertension caused by increased pulmonary blood flow. Increased venous return through aorto-caval shunt caused enlargement of right ventricle, and then developed right ventricle failure, as described before. However, right ventricle hypertrophy as a sign of pulmonary hypertension was not caused by aorto-caval shunt. Histological findings of lung from aorto-caval shunt rats and mice failed to show either pulmonary artery stenosis or plexiform lesion known as characteristic findings of pulmonary hypertension. Then I asked a cooperative laboratory to provide samples of pulmonary artery and vein from pulmonary hypertension model and control lamb. I showed the increase of thrombin receptor expression in both pulmonary artery and vein from model animals, elucidating the relationship of thrombin and pathophysiology of pulmonary hypertension.

Free Research Field

肺高血圧研究

Academic Significance and Societal Importance of the Research Achievements

肺高血圧症はしばしば先天性心疾患に合併する。近年新たな治療薬が開発されているが、肺高血圧症の進行を止める効果的な治療は未だ開発されていない。そこで、肺高血圧症の進行を抑え、症状を軽快する治療薬の開発が望まれる。これまでトロンビンが肺動脈を収縮することを明らかにしてきたが、ことトロンビンが肺高血圧症の進行に関連し、トロンビン受容体拮抗薬が肺高血圧の治療薬として可能性があると仮説を立てて研究を行った。肺高血圧症モデル動物において、肺動脈のトロンビン受容体が増加していることを発見し、仮説が正しいことが明らかになった。