Role of Xuefu Zhuyu decoction in improving pulmonary vascular remodeling by inhibiting endothelial-to-mesenchymal transition.

Abstract

Background: Pulmonary hypertension (pH) is a serious vascular disease characterized by pulmonary vascular remodeling. Xuefu Zhuyu decoction (XFZYD) can potentially improve the latter; however, its mechanism of action requires further investigation.

Methods: Rat models of monocrotaline (MCT)-induced PH and chronic thromboembolic pulmonary hypertension (CTEPH) were employed to investigate whether XFZYD has the potential to improve pulmonary vascular remodeling. After 21 days of XFZYD administration, the right ventricular systolic pressure (RVSP), organ indices, and wall thickness of pulmonary arteries of the rats were measured. Considering the possibility of endothelial-to-mesenchymal transition (EndMT), the specific mechanism of XFZYD in improving pulmonary vascular remodeling was further explored. Immunofluorescence, immunohistochemistry, and western blotting were used to detect the expression of EndMT markers, transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins, hypoxia-inducible factor-1α (HIF-1α), and levels of reactive oxygen species (ROS) in the lung tissues.

Results: XFZYD demonstrated significant efficacy in treating PH, as evidenced by its effects in both the rat models of MCT-induced PH and CTEPH. XFZYD remarkably improved pulmonary vascular remodeling while reducing RVSP and right ventricular hypertrophy. XFZYD has the potential to improve pulmonary vascular remodeling by inhibiting EndMT in the pulmonary vasculature. The underlying mechanism may be closely associated with the inhibition of TGF-β1/Smad and HIF-1α signaling pathways and the reduction of ROS levels in lung tissue by XFZYD.

Conclusion: This study indicates that XFZYD may inhibit EndMT by modulating the ROS/HIF-1α/TGF-β1 signaling pathway, thereby improving pulmonary vascular remodeling. These findings provide a theoretical foundation for the clinical application of XFZYD in PH.