Pulmonary Vascular Endothelial Cells in Lung Diseases: Mechanisms, Therapeutic Strategies, and Future Directions

Pulmonary vascular endothelial cells (VECs) are essential for the normal function of the lung, through maintaining vascular barrier integrity, regulating blood flow, and participating in inflammatory responses to safeguard oxygen exchange and physiological homeostasis. The occurrence and development of various pulmonary diseases all take the injury of pulmonary VECs as an important pathological hub, which directly affects the therapeutic effect and prognosis recovery of patients. The injury mechanisms of pulmonary VECs present multi-dimensional network characteristics, involving inflammation and oxidative stress, genetic factors, cellular senescence, metabolic abnormalities, and immune dysregulation. Due to the unique physiological structure of the lungs, traditional drugs often encounter significant challenges in clinical application such as insufficient targeting, low bioavailability, and systemic side effects. In order to overcome the existing treatment bottlenecks, it is crucial to implement an in-depth analysis of the molecular mechanism of pulmonary VECs injury. This review systematically explores the mechanisms of pulmonary VECs injury, evaluates novel therapeutic strategies targeting pulmonary VECs' dysfunction, and discusses the challenges and future prospects of clinical translation. The goal is to shift pulmonary diseases treatment from symptom management to precise molecular intervention.