The Role Of Autophagy In Anti-inflammatory Effect By Atorvastatin And The Underlying Mechanisms

Atherosclerosis(AS)is regarded as a chronic inflammatory disease of the arterial wall that is associated with various cardiovascular risk factors and immunity mechanisms.It is crucial to investigate the regulatory mechanisms of inflammatory condition and attenuate inflammation in AS.Statins are 3-hydroxy-3-methyglutarylcoenzyme A(HMG-CoA)reductase inhibitors which are prescribed for cardiovascular and cerebrovascular disease patients due to their ability of cholesterol lowering.Accumulating evidence has indicated that statins are also involved in non-lipid-lowing effects,especially their anti-inflammatory effects in AS.However,the underlying mechanisms remain unclear.Recently,macrophages autophagy which may contribute to suppress vascular inflammation is of intense interest.The aim of this study was to elucidate the role of autophagy in the inhibition of inflammatory response in macrophages by atorvastatin.We found that atorvastatin promoted autophagy flow determined by up-regulating the expression of autophagy related protein LC3 II,inducing the formation of autophagosomes and down-regulating the expression of SQSTM1/P62.Atorvastatin also inhibited the secretion of inflammatory factors IL-1? and TNF? induced by LPS in RAW264.7 cells.However,inhibition of autophagy either through knockdown of Atg5,or by treatment with the autophagy inhibitor 3-MA or LY294002,atorvastatin exerted no effect on downregulation of IL-1? and TNF-? secretion.Therefore,we suggest that autophagy induction may work as one of the mechanisms of the anti-inflammatory effects of atorvastatin.Moreover,the AKT/mTOR/P70S6 K signaling pathway may be involved in autophagy activation by atorvastatin.