Paeonol protects mitochondrial injury and prevents pulmonary vascular remodeling in hypoxia.

Mitochondrial injury of pulmonary artery smooth muscle cells (PASMCs) is an important stage in the development of pulmonary arterial hypertension (PAH). Recent studies revealed that Paeonol exerts anti-proliferative effects on vascular smooth muscle cells. However, whether Paeonol is directly involved in mitochondrial injury related to PAH remains unknown. Here, we found that hypoxia-induced mitochondrial injury in vivo was alleviated in the presence of Paeonol. Hypoxia mediated the mitochondrial injuries in PASMCs in vitro, including decreased ATP generation, morphological alterations, mitochondrial polarization and increased reactive oxygen species production, which were suppressed by Paeonol. Our results also indicated that the expression of peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) was regulated by Paeonol. Paeonol caused significant alterations in mitochondrion-dependent apoptosis through PGC-1α in PASMCs. Taken together, these results provide the first evidence confirming the protective effect of Paeonol in mediating mitochondrial injury under hypoxia and elucidating the necessary role of PGC-1α in the effects of Paeonol in inducing PASMC apoptosis.