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

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17616
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Juntendo 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
• Keywords: 肺高血圧症 / 副甲状腺ホルモン / PTH

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.

Free Research Field

肺高血圧症

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。