Difference Between Simvastatin Or Aspirin Single Use And Combination In Regulating Expressions Of Cytokines In Human Umbilical Vein Endothelial Cells

Objective To investigate whether the combination of simvastatin and aspirin or single useof these two medicines contributes differently to the exppressions of cytokines (includingICAM-1, VCAM-1, IL-6, IL-8and eNOS) in human umbilical vein endothelial cells(HUVECs) induced by lipopolysaccharides (LPS) in vitro, and its potential mechanism.Methods HUVECs pre-incubated with different concentrations of simvastatin (1,5,10μmol/L) and/or aspirin (1,2,5mmol/L) with/without PI3K inhibitors (wortmannin,5μmol/L) for30min were induced by100ng/mL LPS for24h in vitro. HUVECs wereharvested and reverse transcription-polymerase chain reaction (RT-PCR) was used to detectthe expressions of ICAM-1、VACM-1、IL-6、IL-8and eNOS mRNA.Results LPS stimulation significantly increased the expressions of ICAM-1、VCAM-1、IL-6and IL-8mRNA and moderately increased the the expression of eNOS mRNA inHUVECs. Simvastatin single use or combinated with aspirin showed much more significanteffect on downregulating the expressions of ICAM-1, VCAM-1, IL-6and IL-8mRNA andupregulating the expression of eNOS than other groups. What’s more, the PI3K inhibitorswortmannin reduced the expressions of ICAM-1and eNOS mRNA significantly, andenhanced the negative effect of simvastatin or aspirin on regulating the expressions ofICAM-1and VCAM-1. In addition, wortmannin partially block the positive effect ofsimvastatin on eNOS expression but failed to abolish the effect of combination. Conclusions HUVECs stimulated by LPS in vitro expressed base levels ofproinflammatory cytokines via PI3K/Akt pathway. Combination of aspirin and simvastatinshowed greater effect on downregulating the expressions of proinflammatory cytokines andupregulate the expression of eNOS than aspirin single use. We concluded that aspirincombined with simvastatin is more effective in anti-inflammation than aspirin orsimvastatin alone.