Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0-10 mM) or β-hydroxybutyrate (BHB) (0-10 mM) for 24 hours prior to evaluating adhesion and adhesion molecule expression. The results (mean ± SE) indicated a 34% ± 11 (p<0.01) increase in U937 adhesion and 31.4% ± 5.2 (p<0.01) increase in THP-1 adhesion to HUVEC monolayers treated with 4 mM AA compared to control. Equal concentrations of BHB also resulted in similar increases in monocyte-EC adhesion. ICAM-1 was significantly increased on the surface of HUVECs and an increase in total protein expression with AA treatment compared to control. The expression level of LFA-1 was increased in monocytes treated with AA, and LFA-1 affinity was altered from low to high affinity following treatment with both AA and BHB. Monocyte adhesion could be blocked when cells were pre-incubated with an antibody to ICAM-1 or LFA-1. Results also show a significant increase in IL-8 and MCP-1 secretion in monocytes and HUVECs treated with 0-10 mM AA. These results suggest that hyperketonemia can induce monocyte adhesion to endothelial cells and that it is mediated via increased ICAM-1 expression in endothelial cells and increased expression and affinity of LFA-1 in monocytes.
- adhesion molecules
- Copyright © 2011, American Journal of Physiology - Endocrinology and Metabolism