Effect of enoxaparin on high glucose-induced activation of endothelial cells.
Clinical and experimental studies indicate that low-molecular-weight heparins reduce inflammation. To uncover the possible mechanisms involved, we investigated the effect of a low-molecular-weight heparin, enoxaparin, on high glucose-induced activation of endothelial cells. Bovine valvular endothelial cells and human endothelial cell line, EA hy926 were cultured in medium containing 5 mM (normal glucose) or 33 mM (high glucose) glucose. Postconfluency, the cells were exposed for 48 h to high glucose in the absence or presence of 16 microg/ml enoxaparin and tested for monocyte adhesion, expression of cell adhesion molecules, and translocation of nuclear transcription factor-kappaB (NF-kappaB), using adhesion assays, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Statistical data revealed that treatment with enoxaparin resulted in a significant decrease in monocyte adhesion, expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, translocation of NF-kappaB, as well as in the level of intracellular reactive oxygen species. These results suggest that enoxaparin reduces the high glucose-induced activation of endothelial cells by inhibiting monocyte adhesion through a mechanism that involves cell adhesion molecules and NF-kappaB.
Manduteanu
Ileana
I
Institute of Cellular Biology and Pathology Nicolae Simionescu, 8, B.P. Hasdeu, P.O. Box 35-14, 79691-, Bucharest, Romania. imanduteanu@simionescu.instcellbiopath.ro
Voinea
Manuela
M
Antohe
Felicia
F
Dragomir
Elena
E
Capraru
Monica
M
Radulescu
Luminita
L
Simionescu
Maya
M
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D019040:E-Selectin / Q000096:biosynthesis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D017984:Enoxaparin / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D020298:U937 Cells; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects
D019040:E-Selectin; D017984:Enoxaparin; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005947:Glucose