BACKGROUND: Recent research shows that Toll like receptor 4 (TLR4) is involved in the occurrence and development ofatherosderosis. The mechanisms of TLR4, MyD88 dependent or MyD88 independent signal transduction during the process ofAS occurrence and development is not clear yet.
OBJECTIVE: To investigate the influence of atorvastatin on expression of lipopolysaccharide-induced (LPS) TLR4 and itsdownstream signal transduction pathway, such as MyD88, TRAF-6, TRAM and TRIF in human umbilical vein endothelial cells(HUVECs), and to study its possible anti-atherosclerotic mechanism.
METHODS: HUVECs was cultured in vitro and stimulated with lipopolysaccharide (LPS), then treated with atorvastatin for 24hours and collected the cells, finally the expression of TLR4, MyD88, TRAF-6, TRAM and TRIF mRNA was measured withreal-time PCR, the expression of TLR4, MyD88 and TRAF-6 protein was analyzed by Western blotting method.
RESULTS AND CONCLUSION: LPS enhanced the expression of TLR4, MyD88, TRAF-6, TRAM and TRIF (vs. normal controlgroup, P < 0.01), atorvastatin decreased the high expression of TLR4, MyD88 and TRAF-6 (vs. model group, P < 0.01) whichwere stimulated by LPS. Atorvastatin can block the high expression of TLR4, and also influence the MyD88-dependent signalingpathway of TLR4. Atorvastatin may exert the function of anti-artherosclerosis by blocking the MyD88-dependent signalingpathway of TLR4.