阻断 A 腺苷受体通过抑制急性心肌梗死后脾脏来源的 MDSC 迁移减轻心肌损伤。
Blocking the A adenosine receptor alleviates myocardial damage by inhibiting spleen-derived MDSC mobilisation after acute myocardial infarction.
机构信息
Department of Cardiology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College, Anhui, China.
Anesthesia Laboratory and Training Center of Wan Nan Medical College, Anhui, China.
出版信息
Ann Med. 2022 Dec;54(1):1616-1626. doi: 10.1080/07853890.2022.2084153.
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.
背景
髓系来源抑制细胞（MDSC）的动员是急性心肌梗死（AMI）中的一个重要免疫事件。A 腺苷受体（AAR）在调节 MDSC 功能方面发挥着关键作用，但它在 AMI 中对 MDSC 动员的具体作用尚不清楚。
方法
在 AMI 患者中，测量循环 MDSC 比例和 AAR mRNA 表达。通过左前降支冠状动脉（LADCA）结扎建立小鼠 AMI 模型。通过流式细胞术和免疫荧光染色（心脏组织）分析 MDSC。通过 qRT-PCR 评估 AAR mRNA 表达。通过 HE 染色检测心肌损伤。通过免疫组化分析心肌细胞凋亡。通过经胸超声心动图评估心脏收缩功能。
结果
在 AMI 患者中，循环 MDSC 比例增加，与 AAR mRNA 表达呈正相关（ = 0.86， < 0.01）。在 AMI 模型小鼠中，循环和梗死心脏中的 MDSC 百分比增加，而脾脏中的 MDSC 百分比减少。MRS-1754 介导的 AAR 抑制减少了循环和梗死心脏中的 MDSC 比例，并防止了 AMI 小鼠脾脏中 MDSC 数量的减少。AAR 阻断抑制心肌细胞凋亡，减轻心肌炎症损伤，改善 AMI 小鼠的心肌收缩功能。在脾切除的小鼠中也发现了类似的结果。此外，脾源性 MDSC 注射增加了梗死心脏中的 MDSC 比例，增加了心肌细胞凋亡，加重了心肌损伤，并降低了 AMI 小鼠的心脏收缩功能。
结论
阻断 AAR 通过抑制 AMI 后脾源性 MDSC 的动员减轻心肌损伤并改善心肌收缩功能。关键信息AMI 后 24 小时内，脾源性 MDSC 动员加重心肌炎症损伤。AMI 后 24 小时内，AAR 促进脾源性 MDSC 动员。阻断 AAR 通过抑制脾源性 MDSC 动员改善心肌收缩功能。
Zotero 插件