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1 From the Division of Endocrinology, Diabetes, and Medical Genetics, Medical University of South Carolina, Charleston; and the 2 Department of Chemistry and Biochemistry, University of South Carolina, Columbia.
PURPOSE. Compared with normal low density lipoprotein (N–LDL), LDL minimally modified in vitro by glycation, minimal oxidation, or glycoxidation (G–, MO–, GO–LDL) decreases survival of cultured retinal capillary endothelial cells and pericytes. Similar modifications occurring in vivo in diabetes may contribute to retinopathy. The goal of this study was to determine whether low concentrations of aminoguanidine might prevent cytotoxic modification of LDL and/or protect retinal capillary cells from previously modified LDL.
METHODS. Minimal in vitro modification of LDL (3 days, 37°C) was achieved with glucose (0, 50 mM), under antioxidant conditions (for N–LDL, G–LDL), or under mild oxidant conditions (for MO–, GO–LDL) in the presence/absence of aminoguanidine (0, 1, 10, 100 µM). Glucose and aminoguanidine were then removed by dialysis. Confluent bovine retinal capillary endothelial cells (n = 13) and pericytes (n = 14) were exposed to LDL (100 mg/l) for 3 days, with and without aminoguanidine (100 µM) in media. Cell counts were determined by hemocytometer.
RESULTS. A decrease in cell counts after exposure to modified compared with N–LDL was confirmed (P < 0.001) but was significantly mitigated if LDL had been modified in the presence of aminoguanidine (P < 0.001). Aminoguanidine was as effective at 1 µM as at the higher concentrations. Aminoguanidine (100 µM) present in culture media conferred no additional protection, and showed slight evidence of toxicity. Aminoguanidine present during LDL modification had no effect on measured glycation or oxidation products, or on LDL oxidizability.
CONCLUSIONS. Very low concentrations of aminoguanidine mitigate toxicity of LDL exposed to stresses that simulate the diabetic environment. This action may contribute to the beneficial effects of aminoguanidine observed in experimental diabetic retinopathy.
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