Rush University Cardiovascular Research Center and Department of Pharmacology, Rush Medical College, Rush University, Chicago, IL 60612, USA.
J Mol Cell Cardiol. 2012 Nov;53(5):668-76. doi: 10.1016/j.yjmcc.2012.08.010. Epub 2012 Aug 19.
The currently used biomarkers for acute myocardial infarction (AMI) are blood creatinine phosphokinase-muscle band (CPK-MB), troponin-T (TnT), and troponin I (TnI). However, no good biomarkers are identified in urine after AMI, because these blood protein biomarkers are difficult to be filtered into urine. In this study, the role of urine microRNAs in the diagnosis of AMI and the mechanism involved were determined. We found that urine miR-1 was quickly increased in rats after AMI with peak at 24h after AMI, in which an over 50-fold increase was demonstrated. At 7 days after AMI, the urine miR-1 level was returned to the basal level. No miR-208 was found in normal urine. In urine from rats with AMI, miR-208 was easily detected. To determine the mechanism involved, we determined the levels of heart-released miR-1 in the liver, spleen and kidney after AMI in rats and found that the kidney was an important metabolic organ. To determine the renal elimination of blood miRNAs, we isolated serum exosomes from rats after AMI and injected these exosomes into the circulating blood of normal rats. We found that the urine miR-1 was significantly increased in exosome-injected animals. Moreover, PKH67-labeled exosomes injected into circulating blood could enter into the kidney tissues and cells, as well as urine. Furthermore, the levels of urine miR-1 were significantly increased in patients with AMI. The results suggest that urine miRNAs such as miR-1 could be novel urine biomarkers for AMI.
目前用于急性心肌梗死（AMI）的生物标志物是血液肌酸磷酸激酶-肌肉带（CPK-MB）、肌钙蛋白-T（TnT）和肌钙蛋白 I（TnI）。然而，AMI 后尿液中没有发现好的生物标志物，因为这些血液蛋白生物标志物很难被过滤到尿液中。在这项研究中，确定了尿液 microRNAs 在 AMI 诊断中的作用及其涉及的机制。我们发现，AMI 后大鼠尿液中的 miR-1 迅速增加，AMI 后 24 小时达到峰值，增加了 50 多倍。AMI 后 7 天，尿液 miR-1 水平恢复到基础水平。正常尿液中未发现 miR-208。在 AMI 大鼠的尿液中，很容易检测到 miR-208。为了确定涉及的机制，我们测定了 AMI 后大鼠心脏释放的 miR-1 在肝脏、脾脏和肾脏中的水平，发现肾脏是一个重要的代谢器官。为了确定血液 miRNAs 在肾脏中的排泄，我们从 AMI 大鼠中分离血清外泌体，并将这些外泌体注入正常大鼠的循环血液中。我们发现外泌体注射动物的尿液 miR-1 明显增加。此外，注入循环血液的 PKH67 标记的外泌体可以进入肾脏组织和细胞以及尿液。此外，AMI 患者的尿液 miR-1 水平显著升高。结果表明，尿液中的 microRNAs，如 miR-1，可以作为 AMI 的新型尿液生物标志物。
