Effects of Radiation on endothelial barrier and vascular integrity.

The excitement of the discovery of radiation as a potent and novel energy source was subdued by the realization that radiation exposure to biological tissues was capable of inducing injuries of a nature not previously encountered. Currently, radiation is an important clinical modality for biological imaging and cancer treatment, but its use continues to be limited by adverse effects on normal tissues. Immediately following radiation exposure, damage to capillaries and small vessels results in an inflammatory response, leading to vascular permeability and edema. Delayed and late effects of radiation on the vasculature include permanent alterations in the in vascular paths, wall thickening, and fibrotic remodeling, and persistent proinflammatory vascular changes are associated with cardiovascular pathologies that can manifest years after radiation exposure. Animal and cell culture models have been used to understand the molecular mechanisms of radiation-induced vascular injury, providing insight into the biological processes leading to the early, delayed, and late effects. This body of research has resulted in the identification of direct effects of radiation on endothelial cell barrier function, viability, and activation. Research has also identified indirect vascular effects of radiation that occur through the induction of inflammation and the release of iron from erythrocytes. Improved understanding of the molecular effects of radiation on the vasculature will aid in the identification of pharmaceutical agents for the prevention, mitigation, and treatment of radiation injuries.