Objective: To study the effect of PCSK9 on the LDL-C metabolism in response to infection and inflammation. Methods:C57B/6J male mice were injected with low dose liposaccharide (LPS) to mimic acute phase responce. Plasma lipids levels were detected. Serum amyloid A levels in peripheral circulation and purified fast protein liquid chromatography (FPLC) fractions have been assayed by ELISA. Real time PCR has been used to measure PCSK9,LDLR,HMGR and other genes mRNA level in mice liver. Results: Low dose LPS treatment induced abundant serum amyloid A secretion and marked changes in lipid and lipoprotein metabolism,including high total cholesterol and triglyceride levels. We explored the effect of LPS on PCSK9 expression,and found LPS resulted in a marked increase in hepatic PCSK9 mRNA levels (2.88-fold increase). Furthermore,we demonstrated that LPS decreased hepatic LDL receptor protein but at the same time hepatic LDL receptor mRNA levels were not decreased. Conclusion: Thus PCSK9 expression stimulated by inflammation led to increased LDL receptor degradation and decreased LDL receptors,and thereby increased serum LDL. The results suggest that proinflammatory states,such as those associated with obesity and insulin resistance,may be associated with upregulated hepatic expression of PCSK9.