Inhibition of glutaminase 1 reduces M1 macrophage polarization to protect against monocrotaline-induced pulmonary arterial hypertension

作者：Xing Chen, Lixiang Li, Yan Deng, Juan Liao, Hui Meng, Limei Liang, Jie Hu, Dongwei Xie, Guizi Liang · 发表于：Immunology Letters · 年份：2025 · DOI：10.1016/j.imlet.2025.106974 · 被引用次数：13 · 研究领域：Pulmonary Hypertension Research and Treatments、Liver Disease and Transplantation、Macrophage Migration Inhibitory Factor

• This study is grounded in theoretical support from previous research and delves into the role of glutaminase 1 (GLS1) in pulmonary arterial hypertension (PAH), exploring its mechanisms and potential therapeutic implications. While prior studies have identified alterations in glutamine metabolism during PAH pathogenesis, the precise mechanisms by which GLS1 regulates macrophage polarization and associated immune-inflammatory responses in the PAH context remain unclear. • Innovation 1: This study is the first to systematically investigate the role of GLS1 in the macrophage phenotype transformation associated with PAH. We demonstrated that GLS1 modulates macrophage M1/M2 polarization, thereby influencing immune-inflammatory responses and vascular remodeling. This finding provides robust theoretical support for considering GLS1 as a novel therapeutic target for PAH. • Innovation 2: We employed the GLS1-specific inhibitor BPTES to analyze its effects on PAH in a rat model. While BPTES has shown significant implications in cancer therapy by inhibiting critical metabolic pathways, reducing tumor growth and metastasis, and enhancing the efficacy of other anticancer drugs, its application to PAH models and pharmacological mechanisms represents a novel approach. Our study highlights the promising therapeutic potential of BPTES for PAH, laying a theoretical foundation for future preclinical and clinical investigations. • Innovation 3: Our research is supported by clinical data obtaine...