miR-223-3p suppresses inflammation to protect cardiomyocytes by targeting NLRP3 in acute myocardial infarction patients

Abstract microRNA (miRNA) had been found played an important role in occurrence and development of acute myocardial infarction (AMI) disease. In this paper, we found that the circulating miR-223-3p in AMI patients was significantly higher than that in unstable angina (UA) patients and healthy people. Univariate and logistic regression analysis showed the circulating miR-223-3p was a protective factor in the occurrence of AMI. We also found that the circulating miR-223-3p was negatively correlated with the serum CK-MB, cTnI, AST, LDH, TNF-α, IL-6, IL-1β and IL-8. The luciferase reporter gene system confirmed that miR-223-3p targeted inhibition of NLRP3 expression in THP-1 and human peripheral blood mononuclear cell (PBMC), and miR-223-3p was negatively correlated with the expression of NLRP3 in the PBMC of AMI patients. In PBMC of healthy people, miR-146a-mimic could increase the expression of NLRP3, but decreased the level of TNF-α secretion. Moreover, H2C9 cells apoptosis by TNF-α in a dose-dependent. In conclusion, these results suggested that miR-223-3p suppressed inflammation to protect cardiomyocytes by targeting NLRP3 in AMI patients.

摘要：微小RNA（microRNA，miRNA）已被证实可在急性心肌梗死（acute myocardial infarction，AMI）的发生与发展过程中发挥关键作用。本研究发现，急性心肌梗死患者外周血中的miR-223-3p表达水平显著高于不稳定型心绞痛（unstable angina，UA）患者及健康人群。单因素及logistic回归分析结果显示，外周血miR-223-3p是急性心肌梗死发生的保护性因素。本研究同时发现，外周血miR-223-3p与血清肌酸激酶同工酶MB（CK-MB）、心肌肌钙蛋白I（cardiac troponin I，cTnI）、天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、白细胞介素1β（IL-1β）及白细胞介素8（IL-8）均呈负相关。荧光素酶报告基因系统实验证实，miR-223-3p可在THP-1细胞及人外周血单个核细胞（human peripheral blood mononuclear cell，PBMC）中靶向抑制核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）的表达，且急性心肌梗死患者外周血单个核细胞中miR-223-3p与NLRP3的表达水平呈负相关。在健康人群的外周血单个核细胞中，miR-146a模拟物（miR-146a-mimic）可上调NLRP3的表达，同时降低肿瘤坏死因子α（TNF-α）的分泌水平。此外，肿瘤坏死因子α（TNF-α）可呈剂量依赖性诱导H9C2细胞凋亡。综上，本研究结果表明，急性心肌梗死患者体内miR-223-3p可通过靶向调控NLRP3通路抑制炎症反应，从而发挥保护心肌细胞的作用。