Abstract | AIMS: METHODS: Human umbilical venous endothelial cells were isolated and cultured to confluence in microtiter plates. After coincubation with monocytes in the presence of 0, 10, or 400 ng ruboxistaurin to achieve PKC beta-specific and -unspecific PKC inhibition, cells were fixed and monocyte adhesion was determined by means of a standardized chemiluminescence assay. Expression of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) was also measured by chemiluminescence methods. RESULTS: Adhesion of monocytes to endothelial cells cultured under hyperglycemic conditions (27.7 mM glucose) was increased by 30.9 +/- 5.1% (p < 0.001) versus endothelial cells cultured under normoglycemic (NG) conditions (5.5 mM). Pretreatment of endothelial cells with 10 nM ( PKC beta-specific concentration) and 400 nM ( PKC beta-unspecific concentration) led to a significant reduction of glucose-induced adhesion of monocytes to endothelial cells that was statistically not different from endothelial adhesion under NG conditions (-7.2 +/- 3.1 and -8.1 +/- 2.6%, respectively; not significant vs NG). A nonsignificant tendency to lower the expression of adhesion molecules was seen with 10 ng of ruboxistaurin. CONCLUSIONS: We conclude that monocyte adhesion to endothelial cells under hyperglycemic conditions is at least mediated by PKC beta activation. Ruboxistaurin is able to suppress this monocyte adhesion even in a PKC beta-specific concentration. Further studies should evaluate these potential effects of ruboxistaurin in vivo.
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Authors | Thomas Kunt, Thomas Forst, Christof Kazda, Oliver Harzer, Martin Engelbach, Mirjam Löbig, Jürgen Beyer, Andreas Pfützner |
Journal | Journal of diabetes science and technology
(J Diabetes Sci Technol)
Vol. 1
Issue 6
Pg. 929-35
(Nov 2007)
ISSN: 1932-2968 [Electronic] United States |
PMID | 19885168
(Publication Type: Journal Article)
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