The Response of the Microvascular System to Radiation: A Review

Abstract

The microvasculature is a ubiquitous organ system having a major role in the pathogenesis of radiation damage to normal tissues. Although the kinetics of radiation damage to endothelial cells is similar to other tissues (as reflected by Do and Dq) the late effect is a manifestation of injury, not only to the endothelial cell population, but also to the basement membrane. Tissue damage is progressive. The initial expression of radiation injury is an increased permeability leading to changes in the extracellular milieu. There is an irregular proliferation of endothelial cells leading to capillaries of irregular diameter and shape. Fibrous proliferation increases the histohematic barrier and is ultimately reflected in a loss of parenchymal cells. Replacement fibrosis progresses until a steady state is reached where the surviving parenchymal cells can be sustained by the microvasculature. The clinical significance depends on the role of the organ system involved. For patients who have medical conditions which adversely effect the stability of the vascular system (hypertension, diabetes, etc.), the expressions of radiation injury may be more severe and increase the morbidity associated with these diseases. Angiogenesis in granulation tissue is less radiosensitive than in steady-state parenchymal tissues. Wound healing is not significantly affected by commonly used therapeutic doses of irradiation, 40-50 Gy delivered 4-6 weeks preoperatively or postoperatively early in the development of the granulation tissue, but may be complicated where a significant degree of fibrosis has developed. The vascular responses leading to telangiectasia were discussed.

Autopsy verifies demyelination and lack of vascular damage in partially reversible radiation myelopathy

“…11 There is an irregular proliferation of endothelial cells, leading to vessels of irregular diameter and shape. 41,42 Archer and Gardiner 43 described a pattern of progressive degenerative vascular changes in response to ionizing irradiation of the retina, ranging from occlusion and microaneurysm formation to microvascular abnormalities such as telangiectasia. As a consequence, the vascular supply to the irradiated structures was altered and resulted in a decreased perfusion.…”

Angiogenesis in patients with craniopharyngiomas

“…Recent studies have shown that combining antiangiogenic therapy with radiation can enhance tumor re- sponse. [45][46][47] Whether this enhancement is attributable to angiogenesis inhibition, endothelial cell radiosensitivity, or tumor cell apoptosis is unclear. 48 -51 In the former scenario, expression of VEGFR-2 in the epithelium and tumoral vasculature of craniopharyngiomas raises the question whether antiangiogenic drugs, such as VEGFR-2 inhibitors, may be used in the treatment of recurrent tumors that are unresponsive to available medical therapies.…”

Low-Dose Ionizing Radiation Stimulates Transcription and Production of Endothelin by Human Vein Endothelial Cells

“…Cytoskeletal rearrangement is known to occur in endothelial cells exposed to [15][16][17][18][19][20]. We conducted a survey of the cytoskeleton in HCAECs at various times after irradiation, including 3 h, at which the impedance measurements suggested that such a rearrangement might take place.…”

“…The ramifications of radiation-induced barrier failure in smaller vessels has been studied, and the result appears to be a modified immune response resulting in the deposition and remodeling of the extracellular matrix, leading to fibrosis (16,17). In the heart, ectopic remodeling of the matrix will have deleterious effects on cardiac function (18,19).…”