Figure 1

Microvasculature as a mediator of (acute) IR damage and as a target for radiation protection. Tissues that are exposed to a high enough dose of IR develop damage and undergo alterations. In the acute setting, IR induces EC loss through apoptosis and other mechanisms. It also affects vascular inflammatory responses in several ways. ECs become activated, expressing cell surface adhesion molecules and enabling neutrophil transendothelial migration. The timing of heightened neutrophil presence may be important for their effect on tissue damage. Additionally, cytokines are secreted and orchestrate further inflammatory responses. There is no clear consensus in the literature on the kind of hemodynamic changes that ensue, although it is known that vascular tone is lost over time. IR exposure also induces senescence which reduces EC proliferative and angiogenic capacity and causes a chronic pro-inflammatory phenotype. However, treating the tissue with a radioprotectant, radiomitigator or therapeutic that counters the microvascular-mediated damage development can result in reduced normal tissue damage.