EFFECTS OF AMINOGUANIDINE ON ADHESION MOLECULE EXPRESSION OF HUMAN ENDOTHELIAL-CELLS

The effect of aminoguanidine (AG) on the expression of adhesion molecu les on nonactivated human umbilical vein endothelial cells (HUVEC) was investigated in vitro, Nonactivated HUVEC cultivated on long-term gly cated fibronectin (FN) as compared to native FN showed a significant u pregulation of intercellular adhesion molecule 1 (ICAM-1), vascular ce ll adhesion molecule I (VCAM-1) and CD31 which could be further promot ed by long-term glycated bovine serum albumin. AG, at a concentration of 0.01 mol/l, caused an upregulation of ICAM-1 of 48 +/- 17.4% in HUV EC cultivated on gelatin. In contrast, VCAM-1 and E-selectin remained unaffected, At this concentration, formation of advanced glycation end products (AGE) was inhibited by 57%, as determined immunologically, a nd by 50%, as verified by AGE-specific fluorescence. A hypothesis conc erning the upregulation of ICAM-1 by AG as compared to VCAM-1 is propo sed relating to its relative redox insensitivity. Our results demonstr ate that the beneficial effect of AG in reducing the risk of accelerat ed development of atherosclerosis in diabetic patients by inhibiting f ormation of AGE on matrix proteins such as FN might be hampered by its tendency to upregulate ICAM-1 on endothelial cells.