Angiogenesis in Lung Regeneration and Aging

Angiogenesis, the formation of new capillary blood vessels, plays a key role in organ development and regeneration, while its dysregulation contributes to disease pathogenesis. In addition to the passive roles of blood vessels in gas exchange and nutrient delivery, endothelial cells regulate tissue homeostasis by secreting angiocrine factors that dictate the behaviors of surrounding cells to build tissue architecture. In the lung, endothelial cells closely interact with alveolar epithelial cells and other resident cells to coordinate signals necessary for alveolar regeneration. During aging, impaired angiogenic responses diminish tissue regeneration and injury repair, increasing susceptibility to chronic lung diseases. In addition to biochemical signals, dynamic changes in the mechanical forces also regulate pulmonary angiogenesis. In this brief review, we highlight the mechanisms by which endothelial cells maintain vascular homeostasis in the lung and how these processes become dysregulated with aging. We also discuss the impact of changes in the micromechanical environment and summarize recently developed new approaches for investigating endothelial cell signaling and cell-cell interactions in the human lung, which leads to the development of future therapeutic strategies.