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KMID : 0858420100120020054
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Korean Journal of Stroke
2010 Volume.12 No. 2 p.54 ~ p.58
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The Effect of Statin Through Vascular Endothelial Growth Factor Expression on Recombinant Tissue Plasminogen Activator-Induced Toxicity in Human Neuronal Cells
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Jeong Joong-Taek
Ahn Jin-Young
Han Moon-Ku
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Abstract
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Background: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) has proven beneficial for acute stroke management. However, rt-PA might also have toxicity on neuronal and endothelial viability. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) has pluripotent actions and beneficial microvascular effect beyond its primary role of reducing serum lipids. The purpose of this study is to investigate the role of statin in reducing human neuronal cell deaths by rt-PA toxicity in an in vitro ischemic condition.
Methods: Human cortical-neuroblastoma hybrid cell line (A1G11) was incubated in hypoxic chamber (951% O2). rt-PA (50 μg/mL) was treated as a toxic agent and simvastatin (10 μM) were administered to investigate its protective effect for the rt-PA toxicity 12 hours before rt-PA treatment. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide] assay was performed to measure the cell viabilities. Vascular endothelial growth factor (VEGF) expression was measured by Western blots.
Results: In an in vitro ischemic condition, the cell viability was decreased and VEGF immunoreactivity was increased. Statin increased VEGF immunoreactivity. An addition of rt-PA treatment in hypoxic condition reduced significantly the cell viability (P<0.05) and VEGF immunoreactivities. Simvastatin pretreatment increased VEGF immunoreactivity after 6 hours (P<0.05) and the cell viability after 6 hours in A1G11 (P=0.023 at 6 h, P=0.002 at 12 h, P=0.019 at 18 h).
Conclusion: These data suggest that statin might reduce rt-PA-induced neuronal cell deaths via an increment of VEGF expression and be helpful to protect neuronal cells in acute ischemic stroke with rt-PA.
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KEYWORD
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Tissue plasminogen activator, HMG-CoA reductase inhibitor (Statin), Vascular endothelial growth factor, Ischemia
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