Zhou Jie, Xia Xiuwen, An Xing, Liu Danping, Zhao Hongyi, Sun Zengtao, Li Weihong, Huang Qingsong
Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Front Med (Lausanne). 2025 Aug 21;12:1639043. doi: 10.3389/fmed.2025.1639043. eCollection 2025.
Traditional studies of pulmonary fibrosis (PF) have focused on alveolar epithelial cells injury and abnormal myofibroblast aggregation, but recent studies have revealed that imbalances in pulmonary capillary homeostasis also play pivotal roles in this disease. The pulmonary microvasculature, composed of aerocyte capillary (aCap) and general capillary (gCap) endothelial cells, forms the core structure of the alveolar-capillary membrane. It performs key roles in gas exchange and nutrient/metabolite transport, while modulating the trafficking of inflammatory factors and immune cells and regulating alveolar damage repair. Abnormal activation of pulmonary microvascular endothelial cells in pulmonary fibrosis, reprogramming of cellular metabolism, secretion of proinflammatory and profibrotic factors, and disruption of pulmonary capillary homeostasis, lead to abnormal remodeling of the pulmonary microvasculature and other pathological changes, promoting the deterioration of PF. Notably, maintaining and restoring normal pulmonary capillary homeostasis is beneficial for improving the local microenvironment of fibrotic lesions and attenuating pathological changes such as hypoxia. In this review, the pathological changes associated with pulmonary capillary homeostasis imbalance in PF are described. Therapeutic directions for restoring pulmonary capillary homeostasis are also proposed with the expectation that they will provide assistance in the treatment of PF.
传统的肺纤维化（PF）研究主要集中在肺泡上皮细胞损伤和异常的肌成纤维细胞聚集上，但最近的研究表明，肺毛细血管内环境稳态失衡在这种疾病中也起着关键作用。肺微血管由气细胞毛细血管（aCap）和普通毛细血管（gCap）内皮细胞组成，形成了肺泡-毛细血管膜的核心结构。它在气体交换和营养物质/代谢产物运输中起关键作用，同时调节炎症因子和免疫细胞的运输，并调节肺泡损伤修复。肺纤维化中肺微血管内皮细胞的异常激活、细胞代谢重编程、促炎和促纤维化因子的分泌以及肺毛细血管内环境稳态的破坏，导致肺微血管的异常重塑和其他病理变化，促进PF的恶化。值得注意的是，维持和恢复正常的肺毛细血管内环境稳态有利于改善纤维化病变的局部微环境，并减轻诸如缺氧等病理变化。在这篇综述中，描述了与PF中肺毛细血管内环境稳态失衡相关的病理变化。还提出了恢复肺毛细血管内环境稳态的治疗方向，期望它们能为PF的治疗提供帮助。
