[Effect of simvastatin on endothelin-1 expression in endothelial cell cultured hypoxically].
OBJECTIVE
To observe the role of simvasatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in synthesis and excretion of endothelin-1 (ET-1) in endothelial cell cultured hypoxically.


METHODS
Human umbilical vein endothelial cells were hypoxically cultured and treated with simvastatin by different concentrations (0, 1.0, 2.5, 5.0, 10.0 micromol/L) and different times (12, 24, 48 h). Mevalonate was used to intervent the effect of simvastatin. Reverse transcription-polymerase chain reaction (RT-PCR)and enzyme-linked immunoadsorbent assay (ELISA) were adopted to measure ET-1 mRNA and ET-1 in supernatant fluid of endothelial cell culture.


RESULTS
(1) There were no changes of ET-1 mRNA and ET-1 expression after the hypoxically cultured endothelial cell were incubated with 1 MICROmol/L simvastatin, but ET-1 expression decreased without significant difference compared to control (0 micromol/L simvastatin) when interfered with 2.5 micromol/L simvastatin. The decreases of ET-1 mRNA and ET-1 expression became more obvious when expression were interfered by 5 micromol/Land 10 micromol/L simvastatin (P < 0.01). (2) ET-1 mRNA and ET-1 expression decreased at 12 h after the endothelial cells were incubated with 10 micromol/L simvastatin, which became more fewer at 24 h and reached the minimum expression at 48 h (P < 0.01). (3) The inhibition effect of simvastatin on ET-1 mRNA and ET-1 expression of endothelial cells could be prevented by mevalonate with concentration of 100 micromol/L.


CONCLUSIONS
Simvastatin can inhibit ET-1 expression in endothelial cell cultured hypoxically.
Xia
Xiu-qiong
XQ
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Cheng
De-yun
DY
Su
Qiao-li
QL
Chen
Xiao-ju
XJ
Yang
Li
L
D015687:Cell Hypoxia; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D019332:Endothelin-1 / Q000378:metabolism*; D006801:Humans; D019821:Simvastatin / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D019332:Endothelin-1; D019821:Simvastatin