Blocking the A_2B adenosine receptor alleviates myocardial damage by inhibiting spleen-derived MDSC mobilisation after acute myocardial infarction

Myeloid-derived suppressor cell (MDSC) mobilisation is an important immune event in acute myocardial infarction (AMI). The A_2B adenosine receptor (A_2BAR) plays key role in regulating MDSC function, but its specific involvement in MDSC mobilisation in AMI remains unclear. In AMI patients, the circulating MDSC ratio and A_2BAR mRNA expression were measured. A mouse AMI model was established by left anterior descending coronary artery (LADCA) ligation. MDSCs were analysed by FACS and immunofluorescence staining (of heart tissue). A_2BAR mRNA expression was assessed by qRT-PCR. Myocardial injury was detected by HE staining. Myocardial cell apoptosis was analysed by immunohistochemistry. Cardiac systolic function was evaluated by transthoracic echocardiography. In AMI patients, the circulating MDSC ratio was increased and positively correlated with A_2BAR mRNA expression (<i>r</i> = 0.86, <i>p</i> &lt; 0.01). In AMI model mice, the percentage of MDSCs was increased in the circulation and infarcted heart and decreased in the spleen. MRS-1754-mediated A_2BAR inhibition decreased the MDSC ratio in the circulation and infarcted heart and prevented the decrease in MDSC number in the spleens of mice with AMI. A_2BAR blockade inhibited myocardial cell apoptosis, alleviated myocardial inflammatory injury, and improved myocardial systolic function in the AMI mouse model. Similar results were found in mice after splenectomy. Additionally, spleen-derived MDSC injection increased the MDSC ratio in the infarcted heart, increased myocardial cell apoptosis, aggravated myocardial injury, and decreased cardiac systolic function in mice with AMI. Blocking A_2BAR alleviates myocardial damage and improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation after AMI. Key MessagesSpleen-derived MDSC mobilisation aggravates myocardial inflammatory injury within 24 h of AMI.A_2BAR promotes spleen-derived MDSC mobilisation within 24 h of AMI.Blocking A_2BAR improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation. Spleen-derived MDSC mobilisation aggravates myocardial inflammatory injury within 24 h of AMI. A_2BAR promotes spleen-derived MDSC mobilisation within 24 h of AMI. Blocking A_2BAR improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation.