A translational study of circulating cell-free microRNA-1 in acute myocardial infarction.
A translational study of circulating cell-free microRNA-1 in acute myocardial infarction.
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DOI：
10.1042/cs20090645
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发表时间：
2010-04-20
期刊：
影响因子：
--
通讯作者：
Zhang C
中科院分区：
文献类型：
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作者：
Cheng Y;Tan N;Yang J;Liu X;Cao X;He P;Dong X;Qin S;Zhang C
MicroRNAs （miRNAs）在包括心血管疾病在内的许多疾病中沉淀。与我们最初的想法相反，mirna存在于循环血液中，并且由于与其他物质结合而相对稳定。目前的转化研究是建立一种方法来确定血液中miRNA的绝对数量，并确定循环无细胞microRNA-1 （miR-1）在急性心肌梗死（AMI）中的潜在应用。结果显示，miR-1是心脏中最丰富的miRNA，也是心脏和肌肉特异性miRNA。在Triton-100体外诱导心肌细胞坏死模型中，我们发现心肌miR-1可以释放到培养基中，并且至少在24小时内保持稳定。在冠状动脉结扎引起的AMI大鼠模型中，我们发现AMI后血清miR-1迅速升高，在6小时达到峰值，miR-1升高超过200倍。AMI后3 d miR-1水平恢复到基础水平。AMI大鼠血清miR-1水平与心肌大小呈正相关。为了进一步验证心肌大小与miR-1水平的关系，我们建立了缺血预处理模型。结果表明，缺血预处理可显著降低缺血再灌注损伤大鼠的循环miR-1水平和心肌大小。最后，AMI患者循环无细胞miR-1水平显著升高，且与血清CK-MB水平呈正相关。结果提示血清miR-1可作为急性心肌梗死的一种新的敏感诊断生物标志物。
MicroRNAs (miRNAs) precipitate in many diseases including cardiovascular disease. In contrast to our original thought, miRNAs exist in circulating blood and they are relatively stable due to binding with other materials. The current translational study is to establish a method to determine the absolute amount of a miRNA in blood and to determine the potential applications of circulating cell-free microRNA-1 (miR-1) in acute myocardial infarction (AMI). The results revealed that miR-1 is the most abundant miRNA in the heart and is also a heart and muscle specific miRNA. In a cardiac cell necrosis model induced by Triton-100 in vitro, we found that cardiac miR-1 can be released into cultured medium and is stable at least for 24 h. In a rat model of AMI induced by coronary ligation, we found that serum miR-1 is quickly increased after AMI with the peak at 6h, in which an over 200-fold increased miR-1 was demonstrated. The miR-1 level was returned to basal level at 3 days after AMI. Moreover, the serum miR-1 level in rats with AMI has a strong positive correlation with the myocardial size. To further verify the relationship between myocardial size and miR-1 level, an ischemic preconditioning model was applied. The result showed that ischemic preconditioning significantly reduced the circulating miR-1 and the myocardial size induced by ischemia-reperfusion injury. Finally, the levels of circulating cell-free miR-1 were significantly increased in patients with AMI and had a positive correlation with serum CK-MB levels. The results suggest that serum miR-1 could be a novel sensitive diagnostic biomarker for AMI.