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B. Fardin, S. Luthra, J. Dong, A. L. Gramajo, A. Neekhra, B. D. Kuppermann, M. C. Kenney; Role of Simvastatin in Inhibiting 7-Ketocholesterol Induced Caspase-3 Activity in Human Microvascular Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):560.
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To determine whether simvastatin, a cholesterol lowering medication, inhibits apoptosis as determined by caspase 3 activity in human microvascular endothelial cells (HMVEC) exposed to 7 ketocholesterol (7kCh).
HMVEC were grown in Medium 131 supplemented with Microvascular Growth Supplement (MVGS). HMVEC were exposed to 7kCh (20 µg/ml) with or without simvastatin (0.001, 0.01, and 0.1 µM) for 24 hours. Caspase-3 activity was measured by a fluorochrome inhibitor of caspase (FLICA) assay.
HMVEC cells treated with only 7kCH had increased caspase-3 activity at 24 hours (p<0.001). Caspase-3 activity induced by 7kCh was reduced by 54% (p<0.01) and 58% (p<0.001) with the addition of simvastatin 0.001 µM and 0.01 µM at 24 hours, respectively. There was no change in 7-kCH induced caspase-3 activity in the cells exposed to simvastatin 0.1 µM for 24 hours.
HMVEC cells exposed to 7kCh undergo apoptosis in a caspase dependent manner as demonstrated by increased caspase-3 activity. This activity can be partially blocked by simvastatin at lower concentrations. Higher concentrations of simvastatin (i.e. 0.1 µM) results in caspase-3 activity similar to cells exposed to 7kCh alone, thus suggesting a toxic effect of higher doses of simvastatin.
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