Zhao Ziwen, Sang Mengmeng, Li Qi, Zhang Hao, Luo Zhiling, Zhang Yunhan, Li Hanlu, Ma Yinbo, Cheng Yuanyuan, Zhuang Donglin, Ju Wenhao, Guo Qiuzhe
Department of Ultrasonography, Fuwai Yunnan Hospital, Chinese Academy of Medical, Sciences/Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, 650102, China.
Department of Immunology, School of Medicine, Nantong University, Nantong, 226019, China.
Biochem Biophys Res Commun. 2025 Feb 16;749:151339. doi: 10.1016/j.bbrc.2025.151339. Epub 2025 Jan 19.
Pulmonary arterial hypertension (PAH) is a syndrome characterized by increased pulmonary vascular resistance and elevated pulmonary artery pressure, ultimately leading to right heart failure and even death. Increasing evidence implicates the fat mass and obesity-associated protein (FTO) in various metabolic and inflammatory pathways; however, its role in pulmonary endothelial function and PAH remains largely unexplored. In this study, we examined the effects of endothelial cell-specific FTO knockout on PAH development. Our results indicate that the absence of FTO in endothelial cells mitigates hypoxia-induced PAH. Mechanistically, FTO deletion reduces endothelial cell adhesion and inflammatory cell infiltration. Single-cell RNA sequencing revealed disruptions in key inflammatory and adhesion pathways, including TNF-α/NF-κB signaling and VCAM1 expression. These findings suggest that targeting endothelial FTO could be a novel therapeutic strategy for PAH by modulating endothelial adhesion and inflammatory responses.
肺动脉高压（PAH）是一种以肺血管阻力增加和肺动脉压力升高为特征的综合征，最终导致右心衰竭甚至死亡。越来越多的证据表明，脂肪量与肥胖相关蛋白（FTO）参与各种代谢和炎症途径；然而，其在肺内皮功能和PAH中的作用在很大程度上仍未得到探索。在本研究中，我们研究了内皮细胞特异性FTO基因敲除对PAH发展的影响。我们的结果表明，内皮细胞中FTO的缺失减轻了缺氧诱导的PAH。从机制上讲，FTO缺失减少了内皮细胞黏附和炎症细胞浸润。单细胞RNA测序揭示了关键炎症和黏附途径的破坏，包括TNF-α/NF-κB信号传导和VCAM1表达。这些发现表明，靶向内皮FTO可能是通过调节内皮黏附和炎症反应来治疗PAH的一种新策略。
