|Title||Dyslipidemia, but not hyperglycemia, induces inflammatory adhesion molecules in human retinal vascular endothelial cells.|
|Publication Type||Journal Article|
|Year of Publication||2003|
|Authors||Chen, W, Jump, DB, Grant, MB, Esselman, WJ, Busik, JV|
|Journal||Invest Ophthalmol Vis Sci|
|Date Published||2003 Nov|
|Keywords||Blotting, Western, Cell Adhesion, Cells, Cultured, Cyclooxygenase Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Electrophoresis, Polyacrylamide Gel, Endothelium, Vascular, Fatty Acids, Unsaturated, Glucose, Humans, Hyperglycemia, Hyperlipidemias, Immunoblotting, Intercellular Adhesion Molecule-1, Leukocytes, Lipoxygenase Inhibitors, Vascular Cell Adhesion Molecule-1|
PURPOSE: The initial determinants of retinal microvascular damage in diabetic retinopathy are not well understood, but are likely to be induced by hyperglycemia and/or dyslipidemia. The purpose of this study was to examine the effect of fatty acids and hyperglycemia on human retinal vascular endothelial (hRVE) cells as a means of mimicking diabetic metabolic disorders.
METHODS: The expression of adhesion molecules in hRVE and human umbilical vein endothelial cells (HUVECs) was assayed by Western blot analysis and confirmed by leukocyte adhesion assay. The mechanisms underlying the induction of adhesion molecules by fatty acids were further investigated by using cyclooxygenase (COX), lipoxygenase (LOX), and P450 monooxygenase (MOX) inhibitors.
RESULTS: Treatment of hRVE cells with the n6 polyunsaturated fatty acids (PUFAs) 18:2n6 and 20:4n6 for up to 24 hours resulted in a significant induction of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 protein levels. In contrast, treatment with high glucose (22 mM) for 24 hours did not affect CAM expression. Induction of CAM by n6 PUFA correlated with enhanced leukocyte binding to hRVE cells. The effect of n6 PUFA on ICAM-1 and VCAM-1 was blocked by an inhibitor of LOX, but not by COX or MOX inhibitors. In contrast to hRVE cells, n6 PUFA did not induce ICAM-1 or VCAM-1 in HUVECs.
CONCLUSIONS: The data obtained in this study demonstrate that acute exposure to linoleic or arachidonic acid, but not hyperglycemia, induces inflammatory adhesion molecule expression in the presence of LOX in microvascular hRVE cells, but not in HUVECs. These results are consistent with the emerging hypothesis recognizing early-stage diabetic retinopathy as a low-grade chronic inflammatory disease.
|Alternate Journal||Invest. Ophthalmol. Vis. Sci.|
|Grant List||EY12601 / EY / NEI NIH HHS / United States |
AI42794 / AI / NIAID NIH HHS / United States
R01 DK043220 / DK / NIDDK NIH HHS / United States
DK43220 / DK / NIDDK NIH HHS / United States
DK065014 / DK / NIDDK NIH HHS / United States
R21 DK065014 / DK / NIDDK NIH HHS / United States