Abstract
Background: Pulmonary hypertension (PH) is characterized by increased pulmonary artery pressure and develops right heart failure. Parathyroid hormone (PTH) is secreted from parathyroid gland and play a critical role in calcium homeostasis. Recent studies have suggested that PTH also acts on the cardiovascular system and affects cardiovascular prognosis. We hypothesized that PTH would play a role in the pathogenesis of PH. Object: This study aimed to investigate the effect of PTH on pulmonary hemodynamics. Method: We measured serum PTH levels in patients who were suspected of PH and underwent right heart catheter examination. We used two types of PH animal models, hypoxia (Hx)-induced PH mouse model and Sugen/hypoxia (SuHx)-induced PH rat model. Hx mice were administered PTH daily for 3 weeks. SuHx rats underwent parathyroidectomy, after which they received SuHx treatment for 10weeks. We measured physical data and right ventricular systolic pressure (RVSP) in these models. We cultured pulmonary artery smooth muscle cell (PASMC) treated with PTH to analyze cell signaling, proliferation and migration. Result: We enrolled 20 participants. PTH concentration was significantly correlated with mean pulmonary artery pressure and pulmonary vascular resistance. PTH treatment exacerbated right ventricular hypertrophy and increased RVSP (33.6mmHg vs. 48.2mmHg) in Hx mice compared with non-treated Hx mice(Figure). Conversely, parathyroidectomy significantly attenuated right ventricular hypertrophy and reduced RVSP (54.2mmHg vs. 29.3mmHg) in SuHx rats compared with sham-operated SuHx rats. PTH promoted migration and proliferation through ERK signaling in PASMC. Conclusion: 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.
Published Version
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