Advanced glycation end products induce apoptosis and procoagulant activityin cultured human umbilical vein endothelial cells

Hyperglycemia and the late products of non-enzymatic glycosylation, called advanced glycation end products (AGEs), play an important role in the devel opment of microvascular complications in diabetes mellitus. Previous studie s have reported that a high glucose environment triggered apoptotic changes in human umbilical vein endothelial cells (HUVECs). Therefore, we investig ated whether AGEs contribute to the development of apoptosis and prothrombo tic activity in HUVECs. After incubation of HUVECs with 0.2, 2.2, 22, 220 a nd 2200 nM of AGE-bovine serum albumin (BSA) from 6 to 48 h, we assayed the degree of apoptosis and procoagulant activity (PCA). There were no signifi cant differences between HUVECs cultured for 48 h with 0.2, 2.2 or 22 nM of AGE-BSA and in controls in the proportion of apoptotic cells (3.5 +/- 0.8% , 3.9 +/- 1.5% and 5.2 +/- 1.1% vs. 2.5 +/- 0.6%). However, the proportion of apoptotic cells increased significantly to 36.7 +/- 9.8% in 220 nM of AG E-BSA, and 72.3 +/- 10.2% in 2200 nM of AGE-BSA (P < 0.001). PCA levels wer e 142 +/- 10 s after 6 h of exposure to 22 nM (P < 0.01), 131 +/- 5 s after 6 h of exposure to 220 nM (P < 0.001), and 106 +/- 4 s after 6 h of exposu re to 2200 nM of AGE-BSA (P < 0.001). These values show that PCA was shorte ned significantly from the basal value of 161 +/- 6 s, and remained below t he basal level until the end of the study. The amount of tissue factor was also significantly increased in 22 and 220 nM of AGE-BSA compared to the co ntrols. In conclusion, this study showed that AGEs could induce apoptosis a nd increase procoagulant activity in cultured HUVECs. We suggest that AGEs can contribute to the development of microvascular complications through ce ll death of HUVECs and functional changes of the blood vessels. (C) 1999 El sevier Science Ireland Ltd. All rights reserved.