Ionizing Radiation Enhances Platelet Adhesion to the Extracellular Matrix of Human Endothelial Cells by an Increase in the Release of von Willebrand Factor

Abstract

The effect of radiation on the secretion of von Willebrand factor by endothelial cells was studied in a three-compartment culture system. The release of von Willebrand factor was significantly increased at 48 h after a single gamma-radiation dose of 20 Gy in both the luminal and abluminal direction by 23 (P < 0.05) and 41% (P < 0.02), respectively. To establish whether the enhanced production of von Willebrand factor affected the thrombogenicity of the extracellular matrix, platelet adhesion to the matrix produced by a monolayer of cultured endothelial cells during 48 h after irradiation was analyzed in a perfusion chamber at high shear rate (1300 s-1). Platelet adhesion was significantly increased by irradiation both in the presence and in the absence of plasmatic von Willebrand factor by 65 (P < 0.05) and 34.5% (P < 0.005), respectively. Incubation of the perfusate with a monoclonal antibody that blocks the binding of von Willebrand factor to platelet GPIb (CLB-RAg 35) resulted in an almost complete inhibition of platelet adhesion. These data indicate that radiation enhances platelet adhesion to the the extracellular matrix by an increase in the release of von Willebrand factor by endothelial cells. This event may be important in early radiation-induced vascular pathology.

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

“…153,154 Endothelial cell loss or endothelial disruption engenders an inflammatory response, which causes endothelial proliferation that increases platelet adherence and thrombus formation. 155,156 In the brain, increased vascular permeability occurs secondary to the loss of tight junctions or increased vesicular activity of the blood-brain barrier. 155,157 Vascular density in cerebral tissue decreases over time.…”

Radiation induced CNS toxicity – molecular and cellular mechanisms

“…Early changes are followed by progressive loss of endothelia. Platelets adhere to exposed matrix leading to the formation of platelet clusters and thrombi (Verheij et al, 1994). This phase occurs within weeks and months and is characterized by vessels partially or fully occluded by thrombi.…”

Venous thromboembolism in hematopoietic stem cell transplant recipients

“…12 HSCT recipients have several identifiable risk factors for thrombosis including malignancy, high-dose myeloablative chemotherapy and immune-modulatory drugs, [13][14][15][16] graft versus host disease (GVHD), [17][18][19] infections, 14,20 indwelling vascular catheters and prolonged immobilization. 14 HSCT is also associated with an 'acquired hypercoagulable state' characterized by inflammation, endothelial damage and activation of endothelium-dependent coagulation factors, increase in von Willebrand factor and platelet adhesion, increased thrombin generation, decreased anti-thrombin levels and decreased levels of anticoagulant proteins such as protein C. [21][22][23][24][25][26][27] graft versus host disease (GVHD) is associated with inflammation that leads to endothelial damage and activation. 28 TNF alpha, an essential mediator in the pathogenesis of GVHD, has been shown to enhance pro-thrombotic alterations on the endothelial cell surface.…”