Piperlongumine attenuates vascular remodeling in hypoxic pulmonary hypertension by regulating autophagy

• Published in: Journal of cardiology Vol. 79; no. 1; pp. 134 - 143
• Main Authors: Ye, Wu, Tang, Tingyu, Li, Zhijun, Li, Xuefang, Huang, Qingdong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2022
• Subjects: Animals; Autophagy; Autophagy, Pulmonary vascular remodeling; Cell Proliferation - physiology; Cells, Cultured; Dioxolanes; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - etiology; Hypoxia - complications; Hypoxia - drug therapy; Hypoxic pulmonary hypertension; Piperlongumine; Pulmonary Artery; Pulmonary vascular smooth muscle cells; Rats; Vascular Remodeling - physiology; Piperlongumine; Autophagy, Pulmonary vascular remodeling; Pulmonary vascular smooth muscle cells; Hypoxic pulmonary hypertension
• ISSN: 0914-5087; 1876-4738
• DOI: 10.1016/j.jjcc.2021.08.023

•Piperlongumine decreased rat right ventricle systolic pressure and right ventricular hypertrophy index.•Piperlongumine increased autophagy flux.•Piperlongumine attenuates vascular remodeling in hypoxic pulmonary hypertension by regulating autophagy.•Piperlongumine treatment may serve as a promising therapy for hypoxic pulmonary hypertension. The aim of this study was to determine the therapeutic effect of piperlongumine on hypoxic pulmonary hypertension. A hypoxic pulmonary hypertension rat model was constructed, primary rat pulmonary artery smooth muscle cells (PASMCs) were isolated, and the proliferation of PASMCs was measured by Cell Counting Kit‑8 assay. The expression of autophagic proteins microtubule-associated protein 1 light chain 3B (LC3B) and P62 were examined by western blot. Autophagic flux in PASMCs was detected by tandem mRFP-GFP-LC3 fluorescence analysis. Hypoxia-induced proliferation of PASMCs was significantly inhibited by piperlongumine exposure. Treatment with piperlongumine elevated LC3B II/LC3B I protein ratio and decreased the expression of P62 protein in both PASMCs and rat lung tissues. Tandem mRFP-GFP-LC3 fluorescence analysis showed that piperlongumine increased autophagic flux in PASMCs. Inhibition of autophagy using 3-methyladenine (3-MA) attenuated the inhibitory effect of piperlongumine on proliferation of PASMCs. Chronic hypoxia exposure led to a significant increase in rat right ventricle systolic pressure, right ventricular hypertrophy, wall thickness and area of pulmonary artery, and muscularization of pulmonary arterioles, which was obviously suppressed by administration of piperlongumine. 3-MA attenuated the alleviating effects of piperlongumine on pulmonary vascular remodeling. Piperlongumine attenuates vascular remodeling in hypoxic pulmonary hypertension by regulating autophagy. Piperlongumine treatment may serve as a promising therapy for hypoxic pulmonary hypertension. [Display omitted]