The Value Of Adenosine A_2B Receptor Mediated Spleen-derived MDSCs Mobilization In Acute Myocardial Infarction

Objective:Mobilization of myeloid-derived suppressor cells（MDSCs）is an important immune event in acute myocardial infarction（AMI）.Adenosine A_2B receptor(A_2BAR)is a G-protein coupled receptor that plays an important role in regulating the activation of MDSCs.However,the specific role of MDSCs in the mobilization of AMI remains unclear.The purpose of this study was to investigate the mobilization of MDSCs after AMI and to clarify the role of MDSCs mobilization in myocardial inflammatory injury.The preliminary mechanism and possible strategies to intervene the mobilization of MDSCs are discussed.To provide a new perspective for the clinical treatment of AMI.Methods:AMI patients who underwent emergency coronary angiography（CAG）and were hospitalized in the cardiology ward of Yi Ji Shan Hospital affiliated to Wan Nan Medical College,were included in this study.Meanwhile,adults without coronary artery disease diagnosed with CAG in our hospital were matched as the control group in a ratio of 1:1.Peripheral blood was collected from both groups and mononuclear cells were isolated.The proportion of MDSCs in peripheral blood and the expression of A_2BAR gene in mononuclear cells were detected respectively,and the correlation between them was discussed.The AMI mouse model was established by ligation of the left anterior descending coronary artery（LADCA）.The proportion of MDSCs in peripheral blood,spleen and heart tissue of mice was detected,and the degree of myocardial inflammatory injury was evaluated.The effect of A_2BAR receptor on MDSCs mobilization in AMI mice was evaluated by the intervention of A_2BAR receptor inhibitor（MS-1754）.To investigate the role and value of spleen in MDSCs mobilization in AMI by excision of spleen and injection of spleen-derived MDSCs,respectively.Results:1.In AMI patients,the proportion of MDSCs in peripheral blood and the expression of A_2BAR gene in mononuclear cells were significantly higher than those of healthy volunteers.Pearson analysis showed that the proportion of MDSCs was positively correlated with A_2BAR m RNA expression（r=0.86,P<0.01）.2.In the AMI mouse model,we found that compared with the control group,the proportion of MDSCs in peripheral blood and infarcted myocardial tissue of LADCA ligation mice was significantly increased,while the proportion of MDSCs in spleen was significantly decreased.Treatments with MRS-1754 significantly reduced the ratio of MDSCs in circulation and myocardial infarction tissue of LADCA ligation mice,and inhibited the mobilization of MDSCs in the spleen of AMI mice.3.The results showed that treatments with MRS-1754 could significantly inhibit the apoptosis of myocardial cells,alleviate the inflammatory damage of myocardial tissue,and improve the myocardial systolic function of AMI mice.Similar results were obtained in mice after splenectomy.In addition,spleen-derived MDSC injection increased the number of MDSC in the myocardial infarction tissue,increased myocardial cell apoptosis,aggravated myocardial injury,and decreased cardiac systolic function in the LADCA ligation mice.Conclusion:Spleen-derived MDSC mobilization was an important factor leading to myocardial apoptosis,aggravating myocardial injury and reducing cardiac systolic function in LADCA ligation mice.While,blocking A_2BAR alleviates myocardial inflammatory damage and improves myocardial systolic function by inhibiting spleen-derived MDSCs mobilization after AMI.