Ferroptosis plays a crucial role in lung diseases, including bronchopulmonary dysplasia (BPD), but its involvement in BPD pathogenesis and impact on pulmonary vascular development remain unclear. This study investigated ferroptosis in BPD and evaluated sodium propionate’s (SP) therapeutic potential in regulating ferroptosis and promoting pulmonary angiogenesis. Serum markers of ferroptosis and oxidative stress were measured in preterm infants (< 32 weeks) with and without BPD. BPD rats and human umbilical vein endothelial cell (HUVEC) models were established through hyperoxia induction. Sprague-Dawley rats were randomly assigned to four experimental groups: normoxia control (CON), normoxia with sodium propionate treatment (CON + SP), hyperoxia-induced BPD model (BPD), and hyperoxia with SP treatment (BPD + SP). In vitro experiments, HUVEC cells were respectively treated with hyperoxia and SP, and transfected with siRNA to detect the role of the SLC7A11/GPX4 pathway. Ferroptosis was evaluated by measuring lipid peroxidation (LPO), malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH). Angiogenesis-related genes (VEGFA, CD31) and angiogenic ability were evaluated by Western blot, RT-PCR and in vitro experiments. Serum LPO and iron levels were significantly elevated in BPD infants. SP alleviated lung injury in BPD rats. SP significantly inhibited PTGS2 expression, decreased ROS, MDA, and LPO levels, and increased GSH in BPD models. It also enhanced mRNA and protein expression of SLC7A11, GPX4, VEGFA, and CD31. Silencing SLC7A11 or GPX4 counteracted SP’s protective effects in hyperoxia-exposed HUVECs. Ferroptosis contributes to BPD pathogenesis. SP effectively inhibits ferroptosis and promotes angiogenesis in experimental BPD models, suggesting a novel avenue for potential combination therapies in BPD treatment.
Xie et al. (Fri,) studied this question.
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