Objective:To study the influence and molecular mechanisms of low shear stress on local vascular endothelial injury and smooth muscle cell proliferation of BALB/c mice. Methods:Thirty BALB/c mice were randomly divided into three groups. Ten mice were taken as the sham-operated group and fed in a normal diet. The model one and model two were established by rapid perivascular collar placement at left common carotid artery(LCCA)and fed in a normal and a high-fat diet,respectively. The body weight was measured periodically. On the third day and eighth week post-operation,the alterations of peak blood flow,end-diastolic diameter of vessels and shear stress of carotid artery were assessed by carotid artery doppler ultrasound. The variations of lipid metabolism were detected by automatic biochemical analyzer during the eighth week post-operation. The pathomorphological and ultrastructural changes of carotid artery were evaluated by hematoxylin-eosin staining and electron microscope,respectively. The gene expression profile changes in the low shear stress blood vessels and in the self-controlled normal shear stress blood vessels were compared by microarray,and then verified by (quantificational real time- polymerase chain reaction,QRT-PCR). GO and KEGG signaling pathway were analyzed and focused on the changes of genes and signaling pathways related to cell migration and proliferation. Results:Compared with sham-operated group,the body weight and serum lipids levels had no significant differences(P > 0.05) in group model one fed with normal diet at the eighth week post-operation. However,the body weight and serum lipids(TC,TG,LDL-C and HDL-C)significantly increased(P < 0.05) in group model two. The shear stress of left common carotid artery-proximal (LCCA-P)was low in group model one and model two. Meanwhile,there were endothelial cell damages,media thickening and endothelial cell vacuolation in the LCCA-P of both group model one and group model two. The lesions in group model two were more serious than those in group model one. But no fatty streaks,plaque formations and lipid accumulations were observed by light microscope and electron microscope. Microarray results suggested that compared with the self-controlled blood vessels from normal shear stress,the blood vessels from low shear stress presented a remarkable miR-27a expression elevation(> 2.0-fold),PPAR signaling pathway down-regulation,MAPK,TGF-β,PI3K/Akt and NF-κB signaling pathway up-regulation,and the cell migration and / or proliferation-related genes up-regulation(TGFB2,END1,CTGF,etc.). The results of QRT-PCR were consistent with microarray. The expression of PPARG decreased to 0.14-fold(P < 0.05,n = 4),TGFB2 and EDN1 increased to 2.51-fold and 1.83-fold,respectively(P < 0.05,n = 4)in the blood vessels from low shear stress. Conclusion:Compared with the blood vessels from normal shear stress,the blood vessels from low shear stress showed the damage of local endothelial cells and media thickening after eight weeks post-operation in BALB/c mice. These changes may be associated with the down-regulation of local PPAR signaling pathways,thereby activating the genes expression and signaling pathways related to cell proliferation and migration.