Establishment of strategy of treatment for the group 3 pulmonary hypertension in a novel animal model

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03666
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Shinshu University
• Principal Investigator: Hanaoka Masayuki 信州大学, 学術研究院医学系, 教授 (20334899)
• Co-Investigator(Kenkyū-buntansha): 北口 良晃 信州大学, 学術研究院医学系(医学部附属病院), 講師 (40447751) ; 和田 洋典 信州大学, 医学部附属病院, 助教(診療) (80848739) ; 安尾 将法 信州大学, 学術研究院医学系(医学部附属病院), 講師 (20402117)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 第3群肺高血圧症 / 肺気腫 / VEGF受容体阻害薬 / 低酸素 / 選択的肺血管拡張薬 / 組織貫通型ホーミングペプチド / ラット

Outline of Final Research Achievements

The present study was to investigate the effects of combined administration of sildenafil and homing peptide (CAR) on the hemodynamic deterioration in the group 3 pulmonary hypertension rat model induced by vascular endothelial growth factor receptor inhibitor (SU5416) plus hypoxia. The mean linear intercept was significantly higher in the SU5416/hypoxia rats than the control rats, suggesting enlargement of airspaces in the SU5416/hypoxia rats. In addition, the mean pulmonary arterial pressure (mPAP) was significantly higher in the rats treated with SU5416/hypoxia than the control rats. However, this increase of mPAP in the SU5416/hypoxia rats was significantly inhibited by the concurrent treatment of sildenafil and CAR with an effective improvement of the pulmonary hemodynamics. The concurrent oral administration of sildenafil and CAR improves pulmonary hemodynamics in the rats exposed simultaneously to VEGF receptor inhibitor and hypoxia.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

第3群肺高血圧症に対する薬物治療の選択肢として、肺血管拡張薬（シルデナフィル）とホーミングペプチド（CAR）併用療法が効果的である可能性が示唆された。第3群肺高血圧症患者に対する薬物療法は確立されておらず、治療方法および治療薬の開発にあたり、血管内皮成長因子（VEGF）受容体阻害薬と持続低酸素による本動物モデルの有用性が示唆された。