Pterostilbene mitigates experimental pulmonary arterial hypertension by inhibiting endothelial-to-mesenchymal transition

作者：Jie Wang, Yu Zhang, Junjun Liu, Fan Jiang, Xiaopei Cui, Weida Lu · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1621700 · 被引用次数：2 · 研究领域：Pulmonary Hypertension Research and Treatments、Nitric Oxide and Endothelin Effects、Phosphodiesterase function and regulation

Background The natural compound pterostilbene (PTE) has multiple cardiovascular protective effects. However, its effects on pulmonary arterial hypertension (PAH)-associated vascular remodeling remain to be elucidated. This study investigated the effects of PTE on monocrotaline (MCT)-induced PAH in rats in vivo and explored the underlying molecular mechanisms in human primary pulmonary arterial endothelial cells (hPAECs) in vitro . Methods Experimental PAH was established by subcutaneous injection of MCT (50 mg/kg) in Sprague-Dawley rats, which were then randomly divided into vehicle or PTE (15 mg/kg via gavage) treatment groups. Endothelial-to-mesenchymal transition (EndMT) was modeled in hPAECs by treating with transforming growth factor-β, tumor necrosis factor-α, and interleukin-1β in combination. Results In rats with MCT-induced PAH, administration of PTE resulted in a reduction in right ventricular systolic pressure, thereby alleviating right ventricular hypertrophy. This was accompanied by mitigation of the remodeling of pulmonary arteries. In vitro , genome-wide mRNA sequencing identified that PTE significantly downregulated the expression of high mobility group AT-hook 2 (HMGA2), a transcription factor involved in the pathogenesis of EndMT. Further, we demonstrated that PTE attenuated EndMT-related changes, including (1) reduced expression of the endothelial cell-specific markers platelet and endothelial cell adhesion molecule 1, and von Willebrand factor; (2) reduced...