Circulating MicroRNAs: Biogenesis and Clinical Significance in Acute Myocardial Infarction

Abstract

Acute myocardial infarction (AMI) causes many deaths around the world. Early diagnosis can prevent the development of AMI and provide theoretical support for the subsequent treatment. miRNAs participate in the AMI pathological processes. We aim to determine the early diagnostic and the prognostic roles of circulating miRNAs in AMI in the existing studies and summarize all the data to provide a greater understanding of their utility for clinical application. We reviewed current knowledge focused on the AMI development and circulating miRNA formation. Meanwhile, we collected and analyzed the potential roles of circulating miRNAs in AMI diagnosis, prognosis and therapeutic strategies. Additionally, we elaborated on the challenges and clinical perspectives of the application of circulating miRNAs in AMI diagnosis. Circulating miRNAs are stable in the circulation and have earlier increases of circulating levels than diagnostic golden criteria. In addition, they are tissue and disease-specific. All these characteristics indicate that circulating miRNAs are promising biomarkers for the early diagnosis of AMI. Although there are several limitations to be resolved before clinical use, the application of circulating miRNAs shows great potential in the early diagnosis and the prognosis of AMI.

Keywords: acute myocardial infarction; biomarkers; challenges; circulating microRNAs; diagnosis.

FIGURE 1

miRNAs related to AMI progression and diagnostic strategies for AMI. There are two causes of AMI with the rupture of atherosclerotic plaques in the coronary arteries as the leading cause. The miRNAs promoting or preventing the formation of AMI are briefly listed. Direct pathological reactions mainly consist of chest pain and chest discomfort. The internal pathological damages are comprised of cardiac injuries, ischemic, hypoxic stress, and so on. There are three diagnostic strategies for AMI, including electrocardiograms (ECGs), coronary angiography and biochemical markers test in blood.

FIGURE 2

The underlying mechanisms of miRNA biogenesis, cellular release and circulation. Pri-miRNAs are generated from miRNA genes with the help of RNA polymerase II and cleaved by Drosha/DGCR8 to form pre-miRNAs. Pre-miRNAs are then transported into cytoplasm and cleaved by Dicer/TRBP. The miRNA duplexs produced are then translated into mature miRNAs. However, only one strand of the miRNA duplex is translated into the mature miRNA. Both pre-miRNAs and mature miRNAs can be released into the bloodstream by several pathways. miRNAs can be released by association with particles, such as lipoprotein complexes (HDL) and RNA-binding proteins (Ago2), or by being packaged in vesicles (exosomes, microvesicles, and apoptotic bodies).