The Mechanisms Of Trim26 On Atherogenesis By Regulating Macrophage Function

Cardiovascular disease(CVD)is a serious threat to human life and health and widely exists worldwide.Atherosclerosis(AS)is the main pathological basis.The formation and development of atherosclerotic lesions are mainly related to the immune response caused by the deposition of lipids in the intima and the infiltration of immune cells such as macrophages.As the main component of atherosclerotic lesions,macrophages play a crucial role in the pathophysiological process of atherosclerosis.The monocytes in the blood are recruited to the intima of the blood vessel wall andthen differentiated into macrophages(Monocyte-derived macrophage,MDMs),Oxidized low-density lipoprotein(ox-LDL)forms a "foam cell" and is an important symbol of atheromatous lesion.Macrophages form foam cells mainly due to Avariety ofreceptors on their surface,such as Scavenger receptor class A(SRA),Scavenger receptor class B(SRB),human leukocyte differentiation Antigen in Scavenger receptor class B family(Cluster of differentiation 36,CD36),Adenosine triphophate(ATP)-binding cassette(ABC)transporter G1(ABCG1)and other lipids were taken or excreted to maintain intracellular lipid balance.Increased uptake or decreased efflux will result in the accumulation of intracellular lipids and the formation of foam cells,which will undergo apoptosis to form necrotic cores and eventually lead to plaque lesions and rupture.Trim26(Tripartite motif 26)is a member of the Trim protein family and has significant features of the Trim family.TRIM26 can act as E3 ubiquitin ligase to regulate the expression of multiple genes.Trim26 plays an important role in immune response,DNA damage repair,DNA reprogramming and other biochemical reactions through its ubiquitination.In general,Trim26 functions as a regulatory factor and plays an important role in the regulation of innate immunity and inflammation.It has been reported that TRIM26 mediates the polyubiquitination and protein degradation of nuclear IRF3’s k48 link,weakens antiviral response,and plays an important role in the inflammatory process.AS is an important inflammatory reaction in the body.There is no literature report on Trim26 regulating the function of macrophages and participating in the occurrence of atherosclerosis.Therefore,in this paper,the regulatory effect of Trim26 on the function of macrophages under oxidative stress was explored based on the function of macrophages,and the role of Trim26 in the process of atherosclerosis was verified by animal experiments.In this paper,the effect of Trim26 on AS was studied through bone marrow transplantation experiment.The results showed that the atherosclerosis process was slowed down in the recipient micetransplanted with Trim26-/-bone marrowcells,which might be due to the decreased ability of macrophages to phagocytose lipids and the level of inflammatory response after deletion of Trim26.The Peritoneal Macrophage of WT and Trim26-/-mice was investigated under oxidative stress and the effect of Trim26 on the phagocytosis function of macrophages was found to be significantly reduced after Trim26 deletion.The expressionof CD36 was down-regulated,while ABCG1 was up-regulated.In addition,the apoptosis of Trim26-/-macrophages was significantly reduced.These results suggest that Trim26 deletion may inhibitthe formation of AS by inhibiting the phagocytic function of macrophages and resisting oxidative stressinduced apoptosis.The results of this study help to reveal the exact mechanism of the occurrence of AS and provide a new potential theoretical basis for the prevention and treatment of AS.