| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
|
|---|
| Research Abstract |
Disseminated intravascular coagulation (DIC) is well-known syndrome as a critical situation because of the complication with thrombosis, bleeding and multiple organ failure. Various molecular markers have been developed to diagnose DIC promptly and accurately. Among many markers, a marker for endothelial injury is still controversial. To establish the perturbed endothelial markers, we focused on modulation of von Willebrand factor (vWF) and related proteins, as the endothelial specific markers. vWF is synthesized as pro-vWF in endothelium, and processed to unique large multimers. Pro-vWF multimers are cleaved to mature-vWF multimers and vWAgII (propolypeptide) dimers, upon the release from cells or the storage into Webel-Palade bodies. We developed monoclonal antibodies against vWF and related proteins, and established ELISA system for measurement of pro-vWF, mature vWF and vWAgII, in experimental conditions and plasma proteins. Pro-vWF was released from cultured human umbilical vein endothelial stimulated by TNF or lipopolysaccharides (LPS). Interestingly, pro-vWF secretion induced by LPS was enhanced in the presence of mononuclear cells from peripheral blood to 3 fold in comparison with LPS alone. Furthermore, plasma pro-vWF antigen levels were increased in patients with DIC, and slightly increased in patients with Diabetes Mellitus associated with angiopathy. Among patients, plasma pro-vWF levels were not co-related with plasma levels of thrombomodulin nor t-PA/PAI complex, which have been established as injured endothelial markers so far.
These results indicate that plasma pro-vWF is not detected in normal conditions, released after cytokine stimulation in inflammatory conditions, and the measurement of pro-vWF might be one of the useful markers for perturbed endothelium.
|
