Effects of rosuvastatin on fibrinolytic system of human umbilical vein endothelial cells in vitro.
BACKGROUND
Besides its lipid-lowering effect, rosuvastatin has an antithrombotic effect, the exact underlying mechanism of which is still unclear. The aim of this study was to investigate the effects of rosuvastatin on the fibrinolytic system, including tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) with its receptor (u-PAR) and plasminogen activator inhibitor-1 (PAI-1), in vascular endothelial cells exposed to oxidized low-density lipoprotein (oxLDL).


METHODS
Human umbilical vein endothelial cells (HUVEC) were cultured and divided into 7 groups: control, rosuvastatin alone (10 nM), oxLDL alone (100 mg/L), oxLDL plus rosuvastatin (0.1, 1.0 and 10 nM, respectively) and oxLDL plus rosuvastatin (10 nM) with mevalonate (100 μM). The lactate dehydrogenase activity and concentrations of t-PA, u-PA, u-PAR and PAI-1 protein in culture medium were measured, whereas the expressions of t-PA, u-PA, u-PAR and PAI-1 mRNA in endothelial cells were detected by real-time polymerase chain reaction at 24 hours after treatment.


RESULTS
Compared with the control group, oxLDL caused a significant increase in lactate dehydrogenase activity. It could reduce the expression of t-PA mRNA and protein (P < 0.05) and increase the expression of PAI-1 mRNA and protein (P < 0.05). Rosuvastatin could protect the endothelial cells, improve t-PA production and reduce PAI-1 production (P < 0.05), whether in unstimulated HUVEC or in HUVEC exposed to oxLDL. The effects of rosuvastatin on the fibrinolytic system could be reversed by mevalonate. No significant differences in u-PA and u-PAR production were seen among different groups.


CONCLUSIONS
Rosuvastatin has protective effects on oxLDL-induced damaged human vascular endothelial cells; its antithrombotic effects may be mediated by the regulation of the fibrinolytic system.
Department of Cardiology (FH, JZ, YL), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China; and Department of Hematology (RG), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Fei
F
He
Jing
J
Zhao
Rong
R
Guo
Ying
Y
Liang
D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D005464:Fluorobenzenes / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D007770:L-Lactate Dehydrogenase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator