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Updated: Jun 26, 2026

Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Sitosterol-Beta mitigates pulmonary hypertension by targeting SPHK1 in mice
Pingping Bai1, Zhuhua Wu2, Yan Qiao3
1Department of Health Management, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, China.
None:
Pulmonary hypertension (PH) is an irreversible and life-threatening disease, characterized by sustainedly elevated pulmonary arterial pressure. The excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and perivascular inflammation are primary pathological features. Sitosterol-Beta is a phytosterol with extensive anti-inflammatory roles. This study aims to investigate the effects of Sitosterol-Beta on PH. In our study, the PH was induced in mouse by chronic hypoxia insult (10% O2) and subcutaneous injection of vascular endothelial growth factor receptor inhibitor SU5416, and Sitosterol-Beta was delivered into mouse via orally taken. Mouse primary PASMCs were cultured with 1% O2 to mimic hypoxic condition, and treated with Sitosterol-Beta. The results revealed that Sitosterol-Beta restrained PH-induced right ventricular systolic pressure increase, right ventricular hypertrophy, thickening and fibrosis of pulmonary artery, and perivascular inflammation. Sphingosine kinase 1 (SPHK1) was screened as the potential target of Sitosterol-Beta. Sitosterol-Beta inhibited SPHK1 expression and sphingosine-1-phosphate (S1P) production in lung. In vitro, Sitosterol-Beta suppressed hypoxia-induced excessive proliferation, migration and phenotypic switching of primary PASMCs, and blocked S1P-mediated inflammation in macrophages. The effects of Sitosterol-Beta on PASMCs were abrogated by overexpression of SPHK1. In conclusion, this study demonstrated that Sitosterol-Beta improved PH in mouse by targeting SPHK1, which may provide novel insights for prevention and therapy of PH.
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