Serum Exosomal MicroRNA-21, MicroRNA-126, and PTEN Are Novel Biomarkers for Diagnosis of Acute Coronary Syndrome

Ling, Hao; Guo, Ziyuan; Shi, Yongfeng; Zhang, Lei; Song, Chunli

doi:10.3389/fphys.2020.00654

Cited by 61 publications

(52 citation statements)

References 29 publications

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“…Moreover, it was demonstrated that exosomal miR-1915-3p, miR-4507, and miR-3656 were decreased in the serum exosomes of AMI patients and these miRNAs were predictive for AMI [ 19 ]. In addition, a recent study found that serum exosomal miR-126 and miR-21 levels were increased in ACS and AMI patients and exosomal miR-126 had a strong correction with the severity of coronary artery stenosis [ 38 ]. The above studies suggest that the expression of circulating exosomal miRNAs is dysregulated in ACS and AMI.…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomal miRNAs as Novel Biomarkers for Stable Coronary Artery Disease

Zhang

Liang

Chen

et al. 2020

BioMed Research International

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Exosomal miRNAs are currently being explored as a novel class of biomarkers in cardiovascular diseases. However, few reports have focused on the value of circulating exosomal miRNAs as biomarkers for stable coronary artery disease (SCAD). Here, we aimed to investigate whether miRNAs involved in cardiovascular diseases in circulating exosomes could serve as novel diagnostic biomarkers for SCAD. Firstly, the serum exosomes were isolated and purified by the ExoQuick reagent and identified by transmission electron microscopy, western blot, and nanoparticle tracking analysis. Then, the purified exosomes were quantified by measuring the exosome protein concentration and calculating the total protein amount. Next, eight miRNAs involved in cardiovascular diseases, miR-192-5p, miR-148b-3p, miR-125a-3p, miR-942-5p, miR-149-5p, miR-32-5p, miR-144-3p, and miR-142-5p, were quantified in circulating exosomes from the control group ( n = 20 ) and the SCAD group ( n = 20 ) by quantitative real-time polymerase chain reaction (qPCR). Finally, the gene targets of the differentially expressed miRNAs were predicted, and the functions and signaling pathways of these targets were analyzed using an online database. The isolated exosomes had a bilayer membrane with a diameter of about 100 nm and expressed exosomal markers including CD63, Tsg101, and Flotillin but negatively expressed Calnexin. Both the exosome protein concentration and total protein amount exhibited no significant differences between the two groups. The qPCR assay demonstrated that among the eight miRNAs, the expression levels of miR-942-5p, miR-149-5p, and miR-32-5p in the serum exosomes from the SCAD group were significantly higher than that from the control group. And the three miRNAs for SCAD diagnosis exhibited AUC values of 0.693, 0.702, and 0.691, respectively. GO categories and signaling pathways analysis showed that some of the predictive targets of these miRNAs were involved in the pathophysiology processes of SCAD. In conclusion, our findings suggest that serum exosomal miR-942-5p, miR-149-5p, and miR-32-5p may serve as potential diagnostic biomarkers for SCAD.

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Section: Discussionmentioning

confidence: 99%

Circulating Exosomal miRNAs as Novel Biomarkers for Stable Coronary Artery Disease

Zhang

Liang

Chen

et al. 2020

BioMed Research International

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“…According to the Kaplan–Meier survival analysis, the 1-year survival rate of patients with high miR-208a levels decreased significantly compared with low miR-208a level group. Further, Ling et al (2020b) showed that the levels of miR-126 and miR-21 in UA and acute myocardial infarction (AMI) patients are significantly higher than those in healthy controls. According to the Gensini score, circulating exosomal miR-126 levels are positively correlated with coronary stenosis in patients with UA and AMI.…”

Section: Cardiovascular Diseases and Exosomal Mirnasmentioning

confidence: 99%

The Role of Exosomes and Exosomal MicroRNA in Cardiovascular Disease

Zheng

Huo

et al. 2021

Front. Cell Dev. Biol.

134

106

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Exosomes are small vesicles (30–150 nm in diameter) enclosed by a lipid membrane bilayer, secreted by most cells in the body. They carry various molecules, including proteins, lipids, mRNA, and other RNA species, such as long non-coding RNA, circular RNA, and microRNA (miRNA). miRNAs are the most numerous cargo molecules in the exosome. They are endogenous non-coding RNA molecules, approximately 19–22-nt-long, and important regulators of protein biosynthesis. Exosomes can be taken up by neighboring or distant cells, where they play a role in post-transcriptional regulation of gene expression by targeting mRNA. Exosomal miRNAs have diverse functions, such as participation in inflammatory reactions, cell migration, proliferation, apoptosis, autophagy, and epithelial–mesenchymal transition. There is increasing evidence that exosomal miRNAs play an important role in cardiovascular health. Exosomal miRNAs are widely involved in the occurrence and development of cardiovascular diseases, such as atherosclerosis, acute coronary syndrome, heart failure (HF), myocardial ischemia reperfusion injury, and pulmonary hypertension. In this review, we present a systematic overview of the research progress into the role of exosomal miRNAs in cardiovascular diseases, and present new ideas for the diagnosis and treatment of cardiovascular diseases.

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“…Zhu et al found that hypoxia-elicited mesenchymal stem cellderived exosomes facilitated cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction [48]. Recently, it showed that serum exosomal microrna-21, microrna-126, and pten are novel biomarkers for diagnosis of acute coronary syndrome [49]. These results demonstrate that exosomal miRNA plays key roles in MI and might provide a novel therapeutic pathway for relieving MI.…”

Section: Discussionmentioning

confidence: 97%

Exosomal miR-218-5p/miR-363-3p from Endothelial Progenitor Cells Ameliorate Myocardial Infarction by Targeting the P53/JMY Signaling Pathway

Yang²,

et al. 2021

Preprint

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BackgroundAccumulating evidence has shown that endothelial progenitor cell-derived exosomes (EPC-Exos) can ameliorate myocardial fibrosis. The purpose of the present study was to investigate the effects of EPC-Exos-derived microRNAs (miRNAs) on myocardial infarction (MI). MethodsA miRNA-Seq dataset of miRNAs differentially expressed between EPCs and exosomes was collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the miRNA expression indicated by miRNA-Seq. Immunofluorescence, cell proliferation and angiogenesis assays were employed to investigate the effects of miRNAs on cardiac fibroblasts (CFs) in vitro. Interactions between miRNAs and their respective targets were examined via immunoblotting, qRT-PCR and luciferase reporter assays. An MI rat model was constructed, and various staining and immunohistochemical assays were performed to explore the mechanisms underlying the miRNA-mediated effects on MI. ResultsmiR-363-3p and miR-218-5p were enriched in EPC-Exos, and miR-218-5p and miR-363-3p mimic or inhibitor enhanced or suppressed CF proliferation and angiogenesis, respectively. miR-218-5p and miR-363-3p regulated P53 and junction-mediating and regulatory protein (JMY) by binding to the promoter region of P53 and the 3’ untranslated region of JMY. Additionally, treatment of CFs with exo-miR-218-5p or miR-363-3p mimic upregulated P53 and down-regulated JMY expression, promoted mesenchymal-endothelial transition and inhibited myocardial fibrosis. Administration of exosomes containing miR-218-5p mimic or miR-363-3p mimic ameliorated left coronary artery ligation-induced MI and restored myocardial tissue integrity in the MI model rats. ConclusionsIn summary, these results show that the protective ability of EPC-Exos against MI was mediated by the shuttled miR-218-5p or miR-363-3p via targeting of the P53/JMY signaling pathway.

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Serum Exosomal MicroRNA-21, MicroRNA-126, and PTEN Are Novel Biomarkers for Diagnosis of Acute Coronary Syndrome

Cited by 61 publications

References 29 publications

Circulating Exosomal miRNAs as Novel Biomarkers for Stable Coronary Artery Disease

Circulating Exosomal miRNAs as Novel Biomarkers for Stable Coronary Artery Disease

The Role of Exosomes and Exosomal MicroRNA in Cardiovascular Disease

Exosomal miR-218-5p/miR-363-3p from Endothelial Progenitor Cells Ameliorate Myocardial Infarction by Targeting the P53/JMY Signaling Pathway

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