上调 microRNA-221-3p 通过抑制 NLRP3/ASC/pro-caspase-1 炎性小体途径激活对冠心病的抗炎作用。
Anti-inflammatory effect of up-regulated microRNA-221-3p on coronary heart disease via suppressing NLRP3/ASC/pro-caspase-1 inflammasome pathway activation.
机构信息
Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine , Shanghai, China.
Cardiovascular Medicine Institute, Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine , Shanghai, China.
出版信息
Cell Cycle. 2020 Jun;19(12):1478-1491. doi: 10.1080/15384101.2020.1754562. Epub 2020 May 6.
OBJECTIVE
As some evidence has demonstrated the role of microRNA-221 (miR-221) on coronary heart disease (CHD), the aim of the present study was to investigate the effect of miR-221-3p on CHD via regulating NLRP3/ASC/pro-caspase-1 inflammasome pathway.
METHODS
Sixty CHD patients and 60 healthy controls were collected to detect the expression of miR-221-3p, NLRP3, ASC, pro-caspase-1 in peripheral blood and the contents of related factors in serum. The rats model of CHD was injected with miR-221-3p agomir or miR-221-3p antagomir to explore its functions in miR-221-3p, NLRP3, ASC and pro-caspase-1 expression, electrocardiogram data, cardiomyocytes apoptosis, myocardial injury, inflammatory reaction and oxidative stress of CHD rats.
RESULTS
MiR-221-3p declined and NLRP3, ASC and pro-caspase-1 raised in CHD. Up-regulated miR-221-3p reduced the change value of J-point and T-wave, decreased NLRP3, ASC and pro-caspase-1 expression, suppressed apoptosis in cardiomyocytes, as well as suppressed myocardial injury, inflammatory reaction and oxidative stress in CHD rats.
CONCLUSION
This study highlights that up-regulated miR-221-3p suppresses the overactivation of NLRP3/ASC/pro-caspase-1 inflammasome pathway and has an anti-inflammatory effect in CHD. Thus, miR-221-3p may serve as a potential target for the treatment of CHD.
目的
有证据表明 microRNA-221（miR-221）在冠心病（CHD）中发挥作用，本研究旨在通过调节 NLRP3/ASC/pro-caspase-1 炎性小体通路来研究 miR-221-3p 对 CHD 的影响。
方法
收集 60 例 CHD 患者和 60 例健康对照者，检测外周血中 miR-221-3p、NLRP3、ASC、pro-caspase-1 的表达及血清中相关因子的含量。采用 miR-221-3p 激动剂或 miR-221-3p 拮抗剂对 CHD 大鼠模型进行注射，探讨 miR-221-3p、NLRP3、ASC 和 pro-caspase-1 表达、心电图数据、心肌细胞凋亡、CHD 大鼠心肌损伤、炎症反应和氧化应激的功能。
结果
CHD 患者 miR-221-3p 降低，NLRP3、ASC 和 pro-caspase-1 升高。上调 miR-221-3p 降低 J 点和 T 波的变化值，降低 NLRP3、ASC 和 pro-caspase-1 的表达，抑制心肌细胞凋亡，抑制 CHD 大鼠心肌损伤、炎症反应和氧化应激。
结论
本研究强调上调 miR-221-3p 抑制 NLRP3/ASC/pro-caspase-1 炎性小体通路的过度激活，在 CHD 中具有抗炎作用。因此，miR-221-3p 可能成为 CHD 治疗的潜在靶点。
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