Search

Cardiovascular disease is a major chronic complication of obesity and diabetes. Due to several patients with obesity and diabetes, it is necessary to urgently explore early diagnostic biomarkers and innovative therapeutic strategies to prevent the progression of cardiovascular diseases. Recently, microRNAs (also known as miRNAs) have emerged as important players in heart disease and energy regulation. MiRNAs are a group of small, highly conserved non-coding RNA molecules that regulate gene expression by suppressing the translation of messenger RNA of target genes or by promoting mRNA degradation. These act as a class of potential biomarkers and may provide key information in diagnosing common diseases such as tumors, tissue damage, and autoimmune diseases. Among all the known miRNAs, microRNA-208 (miR-208) is specifically expressed in myocardial cells and showed close association with the development of cardiac diseases, such as myocardial hypertrophy, cardiac fibrosis, myocardial infarction, arrhythmia, and heart failure. However, the functions and underlying mechanisms of miR-208 in heart are still unclear. In this review, we highlighted the novel insights of miR-208 functions and associated mechanisms in the regulation of cardiac diseases., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Conventional circulating biomarkers of cardiac and skeletal muscle (SKM) toxicity lack specificity and/or have a short half-life. MicroRNAs (miRNAs) are currently being assessed as biomarkers of tissue injury based on their long half-life in blood and selective expression in certain tissues. To assess the utility of miRNAs as biomarkers of cardiac and SKM injury, male Sprague-Dawley rats received a single dose of isoproterenol (ISO); metaproterenol (MET); allylamine (AAM); mitoxantrone (MIT); acetaminophen (APAP) or vehicle. Blood and tissues were collected from rats in each group at 4, 24 and 48h. ISO, MET, and AAM induced cardiac and SKM lesions and APAP induced liver specific lesions. There was no evidence of tissue injury with MIT by histopathology. Serum levels of candidate miRNAs were compared to conventional serum biomarkers of SKM/cardiac toxicity. Increases in heart specific miR-208 only occurred in rats with cardiac lesions alone and were increased for a longer duration than cardiac troponin and FABP3 (cardiac biomarkers). ISO, MET and AAM induced increases in MyL3 and skeletal muscle troponin (sTnl) (SKM biomarkers). MIT induced large increases in sTnl indicative of SKM toxicity, but sTnl levels were also increased in APAP-treated rats that lacked SKM toxicity. Serum levels of miR-133a/b (enriched in cardiac and SKM) increased following ISO, MET, AAM and MIT treatments but were absent in APAP-treated rats. Our results suggest that miR-133a/b are sensitive and specific markers of SKM and cardiac toxicity and that miR-208 used in combination with miR-133a/b can be used to differentiate cardiac from SKM toxicity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background It has been demonstrated that circulating muscle-enriched miR-1 and the cardiac-specific miR-208 and miR-499 might leak out of the necrotic myocardium and release into the circulation during the early stages of acute myocardial infarction (AMI). This study aims to investigate potential predictive value of the three miRNAs in AMI. Methods Plasma samples were taken from 70 AMI patients and 72 healthy controls. The expression levels of target miRNAs were measured by qRT-PCR. Student's t test and χ 2 test were applied to test the significance of the differences between AMI patients and controls. Additionally, a meta-analysis about the prediction accuracy of the three miRNAs in AMI was performed to summarize all the results from available studies. Results The expression of plasma miR-1, miR-208 and miR-499 were all significantly elevated in AMI patients compared with controls. By receiver operating characteristic (ROC) curve analysis, plasma miR-1, miR-208 and miR-499 were demonstrated to be potential biomarkers for the prediction of AMI with AUC values of 0.81, 0.72, and 0.88, respectively. The meta-analysis consisted of nine studies for miR-1, eight studies for miR-208 and eight studies for miR-499. The summary estimates of miR-1, miR-208 and miR-499 were 0.73, 0.80 and 0.83 for sensitivity, 0.82, 0.95 and 0.90 for specificity, 0.84, 0.89 and 0.91 for AUC, respectively. Conclusion In summary, we confirmed the predictive values of plasma miR-1, miR-208 and miR-499 in AMI. In contrast to miR-1, the cardiac-specific miR-208 and miR-499 were supposed to be more reliable as biomarkers in AMI screening and prediction. [ABSTRACT FROM AUTHOR]

ABSTRACT Cardiotoxicity is one of the major safety concerns in drug development. Therefore, detecting and monitoring cardiotoxicity throughout preclinical and clinical studies is important for pharmaceutical companies. The present study was conducted in order to explore a plasma miRNA biomarker for cardiotoxicity in rats. As organ specificity is an important factor for a biomarker, we analyzed the miRNA microarray dataset in 55 organs/tissues in normal male rats. Based on this analysis, 5 miRNAs consisting of miR-208 (heart-specific), miR-1, miR-133a, miR-133b (heart and skeletal muscle-specific) and miR-206 (skeletal muscle-specific) were selected. Next, we evaluated the usefulness of those 5 miRNAs as circulating biomarkers in rats administered with single-dose isoproterenol or doxorubicin. Plasma miR-208 was consistently increased through 24 h after dosing in rats administered with isoproterenol, whereas plasma concentrations of cardiac troponin (cTn) showed transient elevation. In contrast, the plasma levels of miR-1, miR-133a, miR-133a and miR-206 were elevated after treatment with doxorubicin, probably as a result of skeletal muscle toxicity. Additionally, the plasma miR-208 level was elevated even after repeat-dose administration (once daily for 7 days) of isoproterenol under which the pathological condition proceeded to the sub-chronic phase such as fibrosis. Thus, our data suggest that miR-208 is a promising plasma biomarker for cardiotoxicity in rats. Monitoring of plasma miR-208 levels in rats may lead to more accurate evaluation of cardiotoxicity in preclinical studies. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: 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 7days 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. [Copyright &y& Elsevier]