Summary

In diabetes mellitus an increased risk exists for vascular complications.A role for advanced glycation endproducts (AGEs) inthe acceleration of vascular disease has been suggested. N e -(carboxymethyl)lysine (CML)- and methylglyoxal (MGO)-modifiedproteins have been identified as majorAGEs.The interactionof these AGEs with the human endothelial cells and macrophageswas studied. Changes in adhesion molecule expression,i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellularadhesion molecule-1 (ICAM-1) and E-selectin were determinedby cell-bound Elisa on human endothelial cells after incubationwith CML-modified albumin and MGO-modified albumin. Thepresence of the full-length receptor of AGEs (RAGE) and splicevariants of RAGE was determined by specific RT-PCR. In addition,binding studies were performed with CML- and MGOmodifiedalbumin to endothelial cells and P388D1 macrophages.We demonstrated that CML-albumin or MGO-albumin did not induce activation of endothelial cells as measured by the expressionof adhesion molecules, while, under the same conditions,TNF- a did. No specific binding of CML-albumin andMGO-albumin on these cells was found. In contrast to endothelialcells, a specific binding of MGO-albumin to P388D1 macrophageswas demonstrated, which could be competed by ligandsof scavenger receptors. In human umbilical vein and microvascularendothelial cells we found the N-truncated and C-truncatedsplice variants of RAGE.In conclusion, under our experimental conditions no CML- orMGO-albumin-induced increase in adhesion molecule expressionwas found on endothelial cells. In agreement with this,no binding of these AGEs was found to endothelial cells. Theexistence of splice variants of RAGE in endothelial cells mightexplain the lack of interaction of extracellular AGEs with thesecells.