Blocking the A Adenosine Receptor Alleviates Myocardial Damage by Inhibiting Spleen-derived MDSC Mobilisation After Acute Myocardial Infarction

Overview

Journal Ann Med

Publisher Informa Healthcare

Specialty General Medicine

Date 2022 Jun 8

PMID 35675334

Authors

Zongying Yu

Yang Ling

Qiancheng Xu

Yuhan Cao

Shengxing Tang

Cong Fu

Affiliations

Soon will be listed here.

Abstract

Background: Myeloid-derived suppressor cell (MDSC) mobilisation is an important immune event in acute myocardial infarction (AMI). The A adenosine receptor (AAR) plays key role in regulating MDSC function, but its specific involvement in MDSC mobilisation in AMI remains unclear.

Methods: In AMI patients, the circulating MDSC ratio and AAR 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). AAR 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.

Results: In AMI patients, the circulating MDSC ratio was increased and positively correlated with AAR mRNA expression ( = 0.86, < 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 AAR 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. AAR 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.

Conclusion: Blocking AAR 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.AAR promotes spleen-derived MDSC mobilisation within 24 h of AMI.Blocking AAR improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation.

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