Zheng Yuli, Wang Liudi, Zhao Yan, Gong Haibin, Qi Yao, Qi Le
Department of Cardiology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221000, China.
Department of Cardiology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221000, China; Clinical College, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China.
Int J Cardiol. 2024 Mar 15;399:131688. doi: 10.1016/j.ijcard.2023.131688. Epub 2023 Dec 28.
Myocardial infarction (MI) is a cardiovascular diseases, that seriously threatens human life. Signaling lymphocytic activation molecule family member 8 (SLAMF8) has been discovered to regulate the development and function of many immune cells. However, there are limited reports on SLAMF8 in the field of cardiopathy, and its regulatory role also remains unclear.
The mRNA and protein expressions of genes were examined through RT-qPCR and western blot. The infarct size in heart was assessed through TTC staining. The pathological section of heart tissue was evaluated through HE staining. The iron, Fe, MDA and SOD levels were assessed through the corresponding commercial kits. The ROS level was detected through Immunofluorescence (IF) staining. The cell viability and cell apoptosis were assessed through MTT assay and flow cytometry.
Through GEO (GSE84796) database, SLAMF8 exhibited higher expression in heart failure patients. Furthermore, the ischemia/reperfusion SD rat (ischemia/reperfusion, I/R treatment) and H9C2 cell (hypoxia/reoxygenation, H/R treatment) models were set up. The mRNA and protein levels of SLAMF8 were upregulated in ischemia/reperfusion SD rat and H9C2 cell models. In addition, SLAMF8 inhibition alleviated ischemia/reperfusion-induced myocardial injury in SD rats. Moreover, SLAMF8 suppression inhibited ischemia/reperfusion-induced ferroptosis and oxidative stress. Further experiments were performed in H/R stimulated H9C2 cells, and the results showed that SLAMF8 knockdown alleviated H/R-induced cardiomyocyte death, ferroptosis and oxidative stress in H/R-induced cardiomyocyte. Lastly, SLAMF8 activated the TLR4/NOX4 pathway in I/R treated-SD rats or H/R treated-H9C2 cells.
SLAMF8 aggravated ischemia/reperfusion-induced ferroptosis and injury in cardiomyocyte. This discovery may provide a useful bio-target for MI treatment.
心肌梗死（MI）是一种严重威胁人类生命的心血管疾病。信号淋巴细胞激活分子家族成员8（SLAMF8）已被发现可调节多种免疫细胞的发育和功能。然而，关于SLAMF8在心脏病领域的报道有限，其调节作用也尚不清楚。
通过RT-qPCR和蛋白质印迹法检测基因的mRNA和蛋白质表达。通过TTC染色评估心脏梗死面积。通过HE染色评估心脏组织的病理切片。通过相应的商业试剂盒评估铁、Fe、丙二醛和超氧化物歧化酶水平。通过免疫荧光（IF）染色检测活性氧水平。通过MTT法和流式细胞术评估细胞活力和细胞凋亡。
通过GEO（GSE84796）数据库，SLAMF8在心力衰竭患者中表现出较高的表达。此外，建立了缺血/再灌注SD大鼠（缺血/再灌注，I/R处理）和H9C2细胞（缺氧/复氧，H/R处理）模型。在缺血/再灌注SD大鼠和H9C2细胞模型中，SLAMF8的mRNA和蛋白质水平上调。此外，抑制SLAMF8可减轻SD大鼠缺血/再灌注诱导的心肌损伤。此外，抑制SLAMF8可抑制缺血/再灌注诱导的铁死亡和氧化应激。在H/R刺激的H9C2细胞中进行了进一步的实验，结果表明敲低SLAMF8可减轻H/R诱导的心肌细胞死亡、铁死亡和氧化应激。最后，SLAMF8在I/R处理的SD大鼠或H/R处理的H9C2细胞中激活了TLR4/NOX4通路。
SLAMF8加重了缺血/再灌注诱导的心肌细胞铁死亡和损伤。这一发现可能为心肌梗死的治疗提供一个有用的生物靶点。
