Differential effects of radiocontrast agents on human umbilical vein endothelial cells: cytotoxicity and modulators of thrombogenicity.
The endothelium plays a central role in the regulation of blood flow and coagulation. The impact of radiocontrast agents on endothelial cells is therefore potentially clinically important, particularly in percutaneous interventions for acute coronary thrombosis. The effects of radiocontrast agents on endothelial cell viability and determinants of thrombogenicity were studied in human umbilical vein endothelial cells (HUVECs) in vitro. Intercellular tight junctions were assessed using immunofluorescence microscopy and measurement of the transmonolayer electrical resistance (TMR). The concentrations of endothelin-1 (E), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and thrombomodulin (T) were measured in the cell culture media. The ionic, high osmolal radiocontrast agent diatrizoate induced concentration-dependent cell death and an opening of tight junctions with the attendant abolition of the TMR. The concentration of E decreased, vWF increased in the cell culture media, the concentration of PAI-1 and T was not significantly changed by diatrizoate. Radiocontrast agents with reduced osmolality (ioxaglate: ionic; iopamidol: non-ionic) induced an increase in PAI-1 and vWF, but E and T were not significantly changed.


CONCLUSIONS
Radiocontrast agents have differential effects on endothelial cells in vitro including the secretion of modulators of thrombogenesis. The effects are most pronounced in the markedly hyperosmolal compound diatrizoate suggesting a contributory role of hypertonicity. Ioxaglate and iopamidol both increased the prothrombotic factors vWF and PAI-1 to the same degree indicating a similar risk of thrombogenicity between low-osmolal ionic and non-ionic radiocontrast agents in this in vitro model.
Fauser
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Medizinische Universitätsklinik, Abt. III, Bergheimerstr. 58, D-69115 Heidelberg, Germany.
Ullisch
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EV
Kübler
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Haller
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D001777:Blood Coagulation / Q000187:drug effects; D002478:Cells, Cultured; D003287:Contrast Media / Q000633:toxicity*; D003973:Diatrizoate / Q000633:toxicity*; D017097:Electric Impedance; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007483:Iothalamic Acid / Q000633:toxicity; D007485:Ioxaglic Acid / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014841:von Willebrand Factor / Q000378:metabolism
D003287:Contrast Media; D019332:Endothelin-1; D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D014841:von Willebrand Factor; D003973:Diatrizoate; D007483:Iothalamic Acid; D007770:L-Lactate Dehydrogenase; D007485:Ioxaglic Acid