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A critical role of parathyroid hormone in the development of pulmonary hypertension

Research Project

Project/Area Number 19K17616
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionJuntendo University

Principal Investigator

Joki Yusuke  順天堂大学, 医学部, 助教 (40837390)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肺高血圧症 / 副甲状腺ホルモン / PTH / パラトルモン / バイオマーカー
Outline of Research at the Start

肺高血圧症は慢性かつ進行性の難病であり、未だ詳細な病態が解明されていない疾患である。過去の報告から副甲状腺ホルモンであるパラトルモン(PTH)は心血管系疾患に対し影響を及ぼしていることが判明しており、肺高血圧症に対しても関連性を認める可能性がある。臨床研究、基礎実験の双方から肺高血症におけるPTHの役割を明らかにし、血中PTH濃度が重症度や予後予測因子としてのバイオマーカー、PTH管理が新規治療戦略としての利用可能性を検討する。

Outline of Final Research Achievements

We investigated whether parathyroid hormone (PTH) associates with pulmonary hypertension (PH). In a clinical study, serum level of PTH correlated with mean pulmonary arterial pressure and pulmonary vascular resistance. In the basic study, we examined the effect of PTH regulation on pulmonary hemodynamics. In hypoxia-induced PH mouse model, PTH treatment exacerbated right ventricular hypertrophy and increased right ventricular systolic pressure. By contrast, PTH reduction by parathyroidectomy reduced right ventricular overload in sugen/hypoxia-induced PH rat model. We showed PTH receptors are abundant in pulmonary artery smooth muscle in lung, moreover PTH has a direct effect on pulmonary artery smooth muscle cells that PTH promoted migration and proliferation through ERK signaling. Our clinical and experimental data demonstrated a critical role of PTH in the development of PH and suggested that PTH would be a novel therapeutic target for PH treatment.

Academic Significance and Societal Importance of the Research Achievements

本研究成果からPTHが肺血管に直接作用し、PHへ関与している事が示唆された。臨床検討の結果から血中PTH濃度は肺血行動態と相関関係を認めており、今後PH症例のバイオマーカーや予後予測因子として応用できる可能性がある。また基礎検討からPTHの制御はPHに対して有用である結果が得られた。今後PTH制御法が新規PH治療戦略へつながる事が期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2022 2021 2020

All Presentation (10 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Presentation] 肺高血圧症と副甲状腺ホルモンの関連性についての検討2022

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      第266回 日本循環器学会関東甲信越地方会 基礎研究セミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 副甲状腺ホルモンの肺高血圧症へ与える役割の解明2022

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      第51回日本心脈管作動物質学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 副甲状腺ホルモンの 肺高血圧症へ与える役割の解明2021

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      第262回 日本循環器学会関東甲信越地方会
    • Related Report
      2021 Research-status Report
  • [Presentation] 肺高血圧症と副甲状腺ホルモンの関連性についての検討2021

    • Author(s)
      1.Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino Tofogliflozin improves pulmonary hypertension due to heart failure with preserved ejection fraction in mice. AHA Scientific Sessions 2020 Web meeting
    • Organizer
      第50回日本心脈管作動物質学会 , 2021/7/16-17
    • Related Report
      2021 Research-status Report
  • [Presentation] 肺高血圧症と副甲状腺ホルモンの関連性についての検討2021

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      第6回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] A critical role of parathyroid hormone in the development of pulmonary hypertension.2021

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      AHA Scientific Sessions 2021 Web meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tofogliflozin improves pulmonary hypertension due to heart failure with preserved ejection fraction in mice.2021

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] A critical role of parathyroid hormone in the development of pulmonary hypertension.2021

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      第24回日本心血管内分泌代謝学会 YIA候補講演Ⅱ
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Soluble LR11 level is correlates with the severity of pulmonary hypertension due to left heart disease.2020

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      30th International Congress of the European Respiratory Society Web meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tofogliflozin improves pulmonary hypertension due to heart failure with preserved ejection fraction in mice.2020

    • Author(s)
      Yusuke Joki, Hakuoh Konishi, Kiyoshi Takasu, Tohru Minamino
    • Organizer
      AHA Scientific Sessions 2020 Web meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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