Li Shan-Shan, Guo Miao, Zhao Ying, Fan Feifei, Huang Shaoyuan, Yang Houzhi, Chen Xu, Jin Xin
School of Medicine, Nankai University, Tianjin, China.
Tianjin Medical University, Tianjin, China.
Respir Res. 2025 Apr 6;26(1):127. doi: 10.1186/s12931-025-03203-y.
Pulmonary arterial hypertension (PAH) is a progressive, life-threatening condition characterized by increased pulmonary vascular resistance and right ventricular hypertrophy (RVH). Current treatments primarily alleviate symptoms but do not effectively target the underlying molecular mechanisms driving the disease. This study aimed to evaluate the therapeutic potential of R8-modified liposomal delivery of circNFXL1, a circular RNA, in a mouse model of PAH.
R8-circNFXL1 liposomes were synthesized and characterized for their physicochemical properties, including encapsulation efficiency. PAH was induced in C57BL/6 mice using a combination of subcutaneous Su5416 administration and hypoxic exposure. Intranasal delivery of R8-circNFXL1 was performed, and therapeutic effects were assessed using echocardiography and hemodynamic measurements. Molecular mechanisms were explored through analysis of the miR-29b/Kcnb1 axis, a regulatory pathway in PAH.
The R8-circNFXL1 liposomes demonstrated optimal physicochemical properties, including high encapsulation efficiency. Treatment with R8-circNFXL1 significantly reduced RVH, improved cardiac function, and mitigated pulmonary vascular remodeling compared to untreated PAH controls. Molecular analysis revealed that R8-circNFXL1 modulated the miR-29b/Kcnb1 axis, providing insights into its mechanism of action.
R8-circNFXL1 liposomes offer a promising, targeted therapeutic strategy for PAH by addressing underlying molecular mechanisms. This approach has potential implications for developing alternative treatments to improve disease management and outcomes in PAH.
肺动脉高压（PAH）是一种进行性、危及生命的疾病，其特征是肺血管阻力增加和右心室肥厚（RVH）。目前的治疗主要缓解症状，但不能有效针对驱动该疾病的潜在分子机制。本研究旨在评估环状RNA circNFXL1经R8修饰的脂质体递送在PAH小鼠模型中的治疗潜力。
合成R8-circNFXL1脂质体并对其物理化学性质进行表征，包括包封率。使用皮下注射Su5416和低氧暴露相结合的方法在C57BL/6小鼠中诱导PAH。进行R8-circNFXL1的鼻内递送，并使用超声心动图和血流动力学测量评估治疗效果。通过分析PAH中的调节途径miR-29b/Kcnb1轴来探索分子机制。
R8-circNFXL1脂质体表现出最佳的物理化学性质，包括高包封率。与未治疗的PAH对照组相比，R8-circNFXL1治疗显著减轻了RVH，改善了心脏功能，并减轻了肺血管重塑。分子分析表明，R8-circNFXL1调节miR-29b/Kcnb1轴，从而深入了解其作用机制。
R8-circNFXL1脂质体通过解决潜在的分子机制，为PAH提供了一种有前景的靶向治疗策略。这种方法对开发替代治疗方法以改善PAH的疾病管理和预后具有潜在意义。
