Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans

Wang, Guokun; Zhu, Jiaqi; Zhang, Juntao; Li, Qing; Li, Yue; He, Jia; Qin, Yue; Jing, Qing

doi:10.1093/eurheartj/ehq013

Cited by 1,036 publications

(953 citation statements)

References 26 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: 92%

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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: 92%

“…13 However, the sample sizes of these studies were small, and the roles of plasma miRNAs in AMI remain to be determined.…”

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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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“…We have previously found that miR-208a can be used as a serum marker for myocardial ischemia with high sensitivity and specificity [56]. Similarly, a variety of miRNAs change in plasma of patients with PAH.…”

Section: Serum Mirnas Might Serve As Biomarkers For Vascular Diseasementioning

confidence: 99%

miRNAs and lncRNAs in vascular injury and remodeling

Song

Shan

Chen

et al. 2014

Sci. China Life Sci.

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Vascular injury, remodeling, as well as angiogenesis, are the leading causes of coronary or cerebrovascular disease. The blood vessel functional imbalance trends to induce atherosclerosis, hypertension, and pulmonary arterial hypertension. As several genes have been identified to be dynamically regulated during vascular injury and remodeling, it is becoming widely accepted that several types of non-coding RNA, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are involved in regulating the endothelial cell and vascular smooth muscle cell (VSMC) behaviors. Here, we review the progress of the extant studies on mechanistic, clinical and diagnostic implications of miRNAs and lncRNAs in vascular injury and remodeling, as well as angiogenesis, emphasizing the important roles of miRNAs and lncRNAs in vascular diseases. Furthermore, we introduce the interaction between miRNAs and lncRNAs, and highlight the mechanism through which lncRNAs are regulating the miRNA function. We envisage that continuous in-depth research of non-coding RNAs in vascular disease will have significant implications for the treatment of coronary or cerebrovascular diseases. Vascular network is an intricate series of vessels that act as conduits for blood flow. Their injury and remodeling contribute to atherosclerosis, restenosis after angioplasty, hypertension, and other diseases. Molecular mechanisms that underlie vascular injury and remodeling have been intensively studied during the last two decades [13]. As reported, a number of genes have been shown to regulate vascular remodeling and angiogenesis [47]. As it is increasingly acknowledged that several types of non-coding RNAs are also involved in these processes, they have become a new focus of scientific research [8].According to the recent discoveries in the field of RNA, nearly 60% of transcripts seem to lack protein-coding capacity, termed non-coding RNAs [9]. Bioinformatics observations suggest that non-coding RNAs tend to exist in greater numbers in more sophisticated organisms [10]. Functional studies reveal that non-coding RNAs have essential functions in regulating epigenetic processes, and emerge as important regulators of life activities [11]. Among non-coding RNAs, miRNAs and lncRNAs are particularly interesting and are thus intensively investigated. Here, we provide an overview of the extant research findings pertaining to miRNAs and lncRNAs in vascular functional maintenance, injury, remodeling, and angiogenesis. Moreover, we highlight their implications for the treatment of atherosclerosis, hypertension and other vascular-related disease.

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“…S3). Finally, the expression pattern of miRNAs previously shown to be important in heart development and disease was examined: developmentally regulated miR-1, miR-133a, miR-133b, miR-208a, miR-208b, miR-143, and miR-145 [8]; hypertrophy-associated miR-199a and miR-214 [44]; and a circulating serum biomarker of human myocardial infarction, miR-499 [45,46]. These miRNAs all followed the predicted patterns given their roles in cardiomyocyte function, disease, and development (Fig.…”

Section: Mirna Profiling During Hipsc Differentiationmentioning

confidence: 99%

Determination of the Human Cardiomyocyte mRNA and miRNA Differentiation Network by Fine-Scale Profiling

Babiarz

Ravon

Sridhar

et al. 2012

Stem Cells and Development

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To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed an miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification.

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Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans

Abstract: Elevated cardiac-specific miR-208a in plasma may be a novel biomarker for early detection of myocardial injury in humans.

Cited by 1,036 publications

References 26 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

miRNAs and lncRNAs in vascular injury and remodeling

Determination of the Human Cardiomyocyte mRNA and miRNA Differentiation Network by Fine-Scale Profiling

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