Role Of Artery Intima Dendritic Cells Changes In Uremic-accelerated Atherosclerosis ApoE^-/- Mice

Compared with the general population,morbidity and mortality of cardiovascular events significantly increaseddue to artery atherosclerotic of patients with uremia.This has become the first cause of death in patients with uremia.Uremic accelerated atherosclerotic lesion formation time is shorter,the lesion is heavier,and its mechanism is not fully understood.At present,a number of studies have confirmed dendritic cells play a key role in general atherosclerosis,systemic lupus erythematosus accelerated atherosclerosis,Chlamydia pneumoniae pathophysiology of accelerated atherosclerosis and other diseases,so whether it is also involved in uremic accelerated atherosclerosis? No related research has been found and our paper has conducted a preliminary study.Objective : To study the role of artery intima dendritic cells changes in uremic-accelerated Atherosclerosis ApoE-/-mice.Method: took 30 male Apo E-/-mice of only 6 weeks old and randomly divided them into three groups,each group of 10 respectively-the treatment group,uremic group,and atherosclerosis group.All were fed with high fat diet.Then took another 10 old male C57 mice of only 6 weeks old with the same growing background and fed them with normal diet,as the control group.All the mice were given intervention measures for 12 weeks.Western blotting detection of mature DCs in the aorta,flow cytometric detection of mature DCs in the spleen,elisa detection of peripheral blood IL-12p70 levels.Results: uremic group compared with atherosclerosis group,atherosclerotic lesion areas obviously increased(P<0.05),which means uremia group accelerated atherosclerosis and the animal models were successful.MatureDCs in atherosclerotic lesion increased(P<0.05),accompanied by formation ofmore serious atherosclerotic plaques(P <0.05).At present,a large number of studies had demonstrated that DC played an important role in ordinary atherosclerosis.During the disease progression,DCs migrate from the peripheral lymphoid tissues to the arterial wall,which increased arterial disease.We considered that when associated with uremia immune disorder,more DCs migrated into the arterial intima and aggravated artery disease;mature DCs in spleen decreased[CD11c:(3.06±0.07)% vs(5.04±0.13)%,,CD83:(6.96±0.06)% vs(11.48±0.14)%,P<0.05],and IL-12 p70 decreased in peripheral blood[(57.11±3.11)ng/L vs(116±8.72)ng/L(P<0.05)];It demonstrated that in uremia,the number and activity of DCs in peripheral lymphoid organs decreased,which was consistent with uremic immunodeficiency state;and in atherosclerosis,the number and activity of DCs in peripheral lymphoid organs increased,which was consistent with atherosclerosis immune activation.PPARγ is an important receptor expressed on DC,and its role in atherosclerosis is concerned widely.In atherosclerosis,activated PPARγcan inhibit the function of DC,whichplays a role of anti-AS through a variety of ways eventually.We set up PPARγ agonist rosiglitazone treatment group to suppress DC maturation and activation.So we could observe the effect of DC functional status in uremic accelerated atherosclerosis.We found that treatment group compared with uremic group,atherosclerotic lesion areas obviously decreased(P<0.05),mature DCs in atherosclerotic lesion decreased(P<0.05),mature DCs in spleen decreased[CD11c:(1.22±0.02)% vs(3.06±0.07)%,CD83:(3.12±0.10)% vs(6.96±0.06)%,P<0.05 ],and IL-12 decreasedin peripheral blood[(34.25±11.27)ng/L vs(57.11±3.11)ng/L(P<0.05)].However,we observed no significant difference in lipid levels;which indicates rosiglitazone relieved uremic accelerated atherosclerosis related to inhibition of DC,and lipid levels may not be the main reason in uremic accelerated atherosclerosis mice.The mature DCs in artery intima of Rosiglitazone group decreased,which indicate artery intimal hyperplasia related to the number of mature DC in artery intima of uremic accelerated atherosclerosis mice,Rosiglitazone treatment group were reduced mature DCs(P <0.05)in arterial plaque and the spleen compared with uremia group.It means that the treatment group can reduce uremic accelerated atherosclerosisby means ofinhibiting mature DCs in artery intima and spleen.Conclusion: Changes in the number and activity of dendritic cells were relevant with uremia accelerated atherosclerosis in Apo E-/-mice.Increased number of mature DCs in artery intima can accelerate uremia atherosclerosis in Apo E-/-mice.The arterial lesionscan obviously reduce by inhibiting DCs maturation.