Circulating microRNAs are new and sensitive biomarkers of myocardial infarction

D’Alessandra, Yuri; Devanna, Paolo; Limana, Federica; Straino, Stefania; Carlo, Anna Di; Brambilla, Paola G.; Rubino, Mara; Carena, Maria Cristina; Spazzafumo, Liana; Simone, Marco De; Micheli, Barbara; Biglioli, Paolo; Achilli, Felice; Martelli, Fabio; Maggiolini, Stefano; Marenzi, Giancarlo; Pompilio, Giulio; Capogrossi, Maurizio C.

doi:10.1093/eurheartj/ehq167

Cited by 707 publications

(702 citation statements)

References 36 publications

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“…13,21,22 In line with previous evidence, the results of massively parallel sequencing in our study showed that miR-499-5p, miR133a, and miR-208b were elevated >2-fold in patients with AMI when compared with controls ( Figure 2). However, the increase of miR-208a did not reach the threshold of 2-fold change (data are not shown).…”

Section: Discussionsupporting

confidence: 91%

“…However, the increase of miR-208a did not reach the threshold of 2-fold change (data are not shown). D'Alessandra et al 21 were unable to detect an elevation in circulating miR-208a levels after AMI AMI indicates acute myocardial infarction; CI, confidence interval; miRNA, microRNA; and OR, odds ratio. *The relative expression level of miRNAs was normalized to cel-miR-39 and calculated by 2 -ΔCt .…”

Section: Discussionmentioning

confidence: 99%

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Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Huang

Lü

et al. 2014

Circ Cardiovasc Genet

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A cute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. 1 Multiple conventional risk factors and serum atherosclerotic biomarkers have been established for coronary heart disease (CHD). 2 However, advances in genomics and proteomics, especially gene-expression profiling using microarray and quantitative real-time polymerase chain reaction (qPCR), have promoted the generation of many novel molecular biomarkers for AMI with potential clinical values. 3,4 Recently, microRNAs (miRNAs) have attracted extensive interest in the field of cardiovascular diseases. 5 Clinical Perspective on p 198MiRNAs are short, endogenous, noncoding RNAs that regulate gene expressions at the posttranscriptional level by binding to the 3′-untranslated regions of their target mRNAs. 6,7 MiRNAs have now emerged as key regulators of cardiac growth, vascular development, and angiogenesis. 8,9 Recent studies demonstrated that miRNAs can be detected in circulating blood and may be useful as disease biomarkers. 10,11 The levels and identities of circulating miRNAs in cardiovascular diseases have been evaluated in a series of studies. For instance, levels of some vascular and inflammation-associated miRNAs were found to be significantly lower in the plasma of 67 patients with CHD when compared with controls, 12 and the cardiac-specific miRNA, miR-208a, was only detectable in 33 patients with AMI and not Background-Circulating microRNAs ( miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P<0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842-0.900), with a net reclassification improvement of 20.45% (P<0.0001) and an integrated discrimination improvement of 0.16 (P<0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Huang

Lü

et al. 2014

Circ Cardiovasc Genet

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“…There was an increase of more than 1,000-fold in acute myocardial infarction 6,[37][38][39] of miRs-208b and-499. In this condition, they reflect tissue injury and cell death.…”

Section: Microrna As Biomarker In Heart Failurementioning

confidence: 96%

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

Fernandes-Silva¹,

Carvalho²,

Guimarães³

et al. 2012

Arq. Bras. Cardiol.

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Although the impact of exercise on survival of patients with heart failure has been recently questioned, exercise training improves quality of life, functional capacity, inflammation, endothelial and autonomic function. In recent years, interest has increased regarding a group of small non-protein coding RNAs called microRNAs.Studies have shown that the expression of these molecules changes in several pathological conditions, such as myocardial infarction, myocardial ischemia and heart failure, and when clinical improvement occurs, they seem to normalize. With the potential for practical applicability, markers that may be useful in diagnostic and prognostic assessment of heart failure have been identified, such as miR-423-5p. In addition, results of experimental studies have indicated that there are potential therapeutic effects of microRNAs.MicroRNAs are involved in the regulation of gene expression during fetal development and in adult individuals, increasing or decreasing in the heart in response to physiological stress, injury or hemodynamic overload. Thus, the study of the behavior of these molecules in physical exercise has brought important information about the effects of this therapeutic modality and represents a new era in the understanding of heart failure.This review aims to integrate the evidence on microRNAs in heart failure with greater relevance in the study of physical exercise.

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“…It regulates the expression of the beta myosin heavy chain, resulting in the enhancement of myocardial oxygen metabolism and tolerance (24). It has also been demonstrated that the expression levels of miR-499 exhibit a significant change in certain heart diseases, including AMI (25,26).…”

Section: Plasma Levels Of Mir208b (A) and Mir499 (B) Were Significantmentioning

confidence: 99%

Expression of miR-208b and miR-499 in Greek Patients with Acute Myocardial Infarction

Αγιαννιτόπουλος

Pavlopoulou

Tsamis

et al. 2018

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Abstract. Background/Aim: Certain microRNAs (miRs) present in human plasma are candidate biomarkers for cardiovascular diseases, including acute myocardial infarction (AMI). We examined the expression of two cardiac-specific miRs (miR-208b and miR-499) MicroRNAs (miRs) are evolutionary small endogenous, noncoding, single-stranded RNAs involved in the regulation of gene expression at the post-transcriptional level (1). They possess an important role in multiple biological processes by binding to their target mRNAs and altering the protein expression of their candidate targets (2). Circulating miRs detected in serum or plasma, are actively secreted in macrovesicles or exosomes from different cell types (3), including cardiomyocytes. Elevated mRNA expression levels have been involved in numerous human pathologies including cardiovascular diseases (4).Acute myocardial infarction (AMI) is the acute necrosis of myocardial tissue due to persistent and severe ischemia, and remains a leading cause of morbidity and mortality worldwide (5). Accurate and rapid diagnosis is crucial for the clinical management and prognosis of AMI (6). Thus, exploration of new potential biomarkers that will contribute in this direction is particularly important. Although the circulating levels of cardiac troponin proteins are currently regarded as the most prominent biomarkers for the diagnosis of AMI, measurable amounts of troponins are not usually released from damaged myocardium earlier than 4-8 h after the onset of symptoms (6, 7). In contrast, the levels of circulating plasma miRs can be measured rapidly using realtime PCR, offering two main advantages over standard antibody-based assays: increased sensitivity and specificity. Several studies have already considered circulating cardiacspecific or -enriched miRs as new biomarkers for the early diagnosis of .In fact, the vast majority of these studies have been performed in Asian populations, while limited studies from European populations are also available (12). Consequently, better validation through larger studies is required for the establishment of miRs as biomarkers in clinical practice. Based on the elegant study of Huang et al. (13) who showed that miRNA expression levels exhibit population differences, and the recorded dysregulation of two specific myocardialderived miRNAs in AMI patients (14, 15), we decided to further investigate their expression in a Caucasian population. Specifically, the purpose of this study was to 313

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Circulating microRNAs are new and sensitive biomarkers of myocardial infarction

Cited by 707 publications

References 36 publications

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

Expression of miR-208b and miR-499 in Greek Patients with Acute Myocardial Infarction

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