Structure-function relationship of the endothelial cell membrane receptors playing in the anti-thrombotic properties.

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The anti-thrombotic properties of the endothelium are the most important systems to maintain the vascular blood fluidity. The aim of this project is to clarify the structure-function relationship of the several receptors on the endothelial cell membrane playing in the anti-thrombotic functions. Here we studied the following subjects :(1)Effect of adenosine (Ado) on the tissue factor (TF) expression induced by lipopolysaccharide and or thrombin. Ado was found to inhibit TF expression via stimulating the endothelial nitric oxide synthase (eNOS) mRNA expression and also enzymatic activity. (2) Effect of aspirin and sodium salicylates (Sal) on the anti-thrombotic activity of Ado. Sal was shown to enhance the Ado production and increased extracellular level of Ado stimulates Ado receptor resulting in the decrease of TF expression in the thrombin-stimulated endothelial cells Sal and Ado may inhibit the NF_<-κ>B activation in the cells. (3) Gene structure analysis of the endothelial protein C receptor (EPCR) and thrombomodulin (TM) of the patients who have thrombotic episodes to understand the structure-function relationship of EPCR and TM. A series of these studies may highlight the molecular bases of the anti-thrombotic properties of the endothelial cells.