Effect Of Different Type Of Stress On Atherosclerosis And Inflammation In Apolipoprotein E Gene Deficient Mice

Objective:To investigate whether atherosclerotic plaque instablilty and inflammation is increased and the related mechanisms by studying the effect of different type of stress in apolipoprotein E gene deficient mice.Method:According to weight,28 apolipoprotein E gene deficient(ApoE^-/-) mice were randomly divided in to four groups,control group(C),the physical stress group(PS),the psychological stress group(ES) and chronic multi-stress group(CS).The atherosclerosis and the stress models were made.The levels of serum total cholesterol(TC),intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) in ApoE^-/- mice were detected.The expression of ICAM-1 and VCAM-1 in arteria anonyma were determined by immunohistochemistry.Immunohistochemistry was also used to identify CD68⁺ macrophages,CD3⁺ T-lymphocytes andα-smooth muscle actin.Result:â‘ the weight and level of serum TC in CS group were significantly increased than other groups(P<0.05 respectively),as well as that in ES group increased than PS group and C group,the weight and level of serum TC were not significant different between PS group and C group.â‘¡Advanced atherosclerotic plaques were observed in all groups.Compared with other groups,most plaques area,calcification area,instable plaque,ratio of spontaneous plaques rupture were observed in the CS group.Those in ES group were more than PS group and C group.â‘¢The CS group had more macrophages,T-lymphocytes,reducedα-smooth muscle actin than other groups.The dencity of macrophages,T-lymphocytes in arteria anonyma in ES group were more than that in PS group and C group,and the dencity ofα-smooth muscle actin were lower than that in PS group and C group.â‘£The serum level of sICAM-1 and the expression of ICAM-1 in arteria anonyma in the CS group were significantly increased than other groups(P<0.01 respectively).The serum level of sICAM-1 and the expression of ICAM-1 in the ES group were significantly increased than PS group and C group(P<0.C, respectively).There was positive relation between the serum level of sICAM-1 and the expression of ICAM-1 in arteria anonyma.⑤The serum level of sVCAM-1 and the expression of VCAM-1 in arteria anonyma in the CS group were significantly increased than other groups(P<0.01 respectively).The serum level of sVCAM-1 and the expression of VCAM-1 in the ES group were significantly increased than PS group and C group(P<0.01 respectively).There was positive relation between the serum level of sVCAM-1 and the expression of VCAM-1 in arteria anonyma.Conclusion:(1)chronic multi-stress ApoE^-/- mice model was a ideal model for the study of the relation between stess and atherosclerosis.(2)These data indicated that psychological stress enhanced inflammatory reaction,and these changes may contribute to increased instability in atherosclerotic plaques.(3)It maybe feasible for stress group to use serum inflammatory markers to deduce the inflammation in plaque,even to deduce its instability.(4)Treating psychological stress may prevent the development and the progression of atherosclerosis.