Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction

Cortez-Dias, Nuno; Costa, Marina C.; Carrilho‐Ferreira, Pedro; Silva, Doroteia; Jorge, Cláudia; Calisto, C.; Pessoa, Teresa; Martins, Susana; Sousa, João de; Silva, Pedro Canas da; Fiúza, Manuela; Diogo, António Nunes; Pinto, Fausto J.; Enguita, Francisco J.

doi:10.1253/circj.cj-16-0568

Cited by 86 publications

(71 citation statements)

References 38 publications

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“…Recently, miRNA have been identified as critical molecular targets in the process of myocardial injury and recovery [20–22]. Our study demonstrates that miR-21 overexpression contributes to enhanced invasion and proliferation of BMSCs, thereby significantly enhancing their ability to repair myocardial injury by anthracyclines.…”

Section: Discussionmentioning

confidence: 60%

Bone marrow-derived mesenchymal stem cells overexpressing miR-21 efficiently repair myocardial damage in rats

et al. 2017

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ObjectiveWe investigated the ability of bone marrow derived mesenchymal stem cells (BMSCs) overexpressing microRNA-21 (miR-21) to repair cardiac damage induced by anthracyclines in rats.MethodsSprague-Dawley (SD) rats of 2~3 weeks old were selected to isolate and culture BMSCs. A lentivirus harboring pLVX-miR-21 was generated and transfected into rat BMSCs. The rats were assigned into an untreated negative control group, and groups injected with adriamycin alone or with adriamycin followed by BMSCs, pLVX-BMSCs or pLVX-miR-21-BMSCs (n = 10 each). Proliferation and migration of cells were detected by cholecystokinin-8 (CCK- 8) and transwell. MiR-21 expression, mRNA expressions of B cell lymphoma 2 (Bcl2), BAX (BCL-2-associated X protein) and vascular endothelial growth factor (VEGF) were tested by qRT-PCR. Western blotting was applied to detect protein expressions of Bcl-2, Bax and VEGF.ResultsUsing CCK- 8 and transwell assays, we found that pLVX-miR-21-BMSCs, which overexpressed miR-21, exhibited greater proliferation and migration than untransfected BMSCs or pLVX-BMSCs. Ultrasonic cardiograms and immunohistochemical analysis demonstrated that among the five groups, the pLVX-miR-21-BMSC group exhibited the most improved heart function and enhanced angiogenesis. Moreover, the pLVX-miR-21-BMSC group showed enhanced expression of Bcl-2, VEGF and Cx43 and reduced expression of Bax, BNP and troponin T.ConclusionThese findings suggest miR-21 overexpression enhanced the proliferation, invasiveness and differentiation of BMSCs as well as expression of key factors (Bcl-2, VEGF and Bax) essential for repairing the cardiac damage induced by anthracyclines and restoring heart function.

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Section: Discussionmentioning

confidence: 60%

Bone marrow-derived mesenchymal stem cells overexpressing miR-21 efficiently repair myocardial damage in rats

et al. 2017

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“…There are strong correlations between the clinical and molecular assays in early diagnosis and less-invasive and reliable diagnostic procedures, depending on the situation. Recent studies reported that the most focused cardiac-specific miRNAs are microRNA-208b-3p, microRNA-499a-5p, microRNA-133 and microRNA-1 (Olivieri et al, 2013;Wang et al, 2013;Olivieri et al, 2014;Yao et al, 2014;Cortez-Dias et al, 2016). It has been found that microRNA-133a-3p levels are associated with myocardial salvage, infarct size and microvascular obstruction (Deng and Zhong, 2016).…”

Section: Discussionmentioning

confidence: 99%

Molecular miR-19a in Acute Myocardial Infarction: Novel Potential Indicators of Prognosis and Early Diagnosis

Mansouri

Mohammadzad

2020

Asian Pac J Cancer Prev

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Objective: Due to the increasing annual incidence rate of disability and mortality in patients with acute myocardial infarction (AMI), the need for an appropriate diagnostic tool has become a crucial urgent issue. An increase in biomarkers and protein levels in response to AMI can be used as a predictive biomarker with different sensitivities and specificities. This study aimed at investigating the role of miR-19a as a biomarker with acceptable sensitivity and specificity for early diagnosis of AMI. Methods: We studied 175 patients with AMI admitted within 12 h of symptom onset and 90 healthy subjects as control group. Patients were divided into two groups, including group I (normal vessels and no significant artery stenosis) and primary percutaneous coronary intervention (PCI) group II (patients with more than 50% stenosis in vessels and severe atherosclerosis) diagnosed by angiography. The expression level of miR-19a was evaluated by the real-time polymerase chain reaction and other serum chemistries were also analyzed. Results: The results demonstrated that circulating miR-19a levels were significantly increased in patient groups compared to the control group (2.88 ± 1.06 vs. 5.93 ± 1.28, P<0.0001). We also found that miR-19a levels were higher in group II (134.62-fold) than group I (15.42-fold). The upper levels of miR-19a were significantly correlated with the increased serum levels of CK-MB (ρ=0.29, P<0.0001), CTn I (ρ=0.4, P<0.0001) and creatinine (ρ=0.27, P<0.0001). In addition, Receiver Operating Characteristic (ROC) analysis revealed that circulating miR-19a had considerable diagnostic accuracy for the patients with normal vessel with an AUC of 0.930 (95% CI: 0.697-0.765) and for PCI patients with an AUC of 0.966 (95% CI: 0.748-0.784). Conclusion: Circulating miR-19a possibly has prognostic value to be used as a promising molecular target for early diagnosis and prognosis of AMI.

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“…[25][26][27][28] A previous study has shown that miR-122 regulates apoptosis in cutaneous TCell lymphoma through the p53/Akt signaling pathway. 40 Additionally, miR-122 has been found to promote cardiac apoptosis in Pax-8-/-mice and to affect CCK-8 expression in H9c2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22][23] In our previous study, 24 the differential miRNA prole in a rat model of post-infarction heart failure showed that miR-122, as one of the most abundantly expressed miRNAs, is markedly upregulated during the development of heart failure, which revealed its potential role in this complex pathological process. Furthermore, miR-122 has been applied as a novel biomarker for many cardiovascular diseases such as acute coronary syndrome [25][26][27][28] and as a predictor of outcome. 29 However, whether miR-122 involves in Ang II-induced apoptosis and the mechanisms by which miR-122 contributes to apoptosis remain unclear.…”

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confidence: 99%

The impact of microRNA-122 and its target gene Sestrin-2 on the protective effect of ghrelin in angiotensin II-induced cardiomyocyte apoptosis

et al. 2018

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Ghrelin with n-octanoylated serine 3 residue is a peptide hormone with well-known cardioprotective properties.MicroRNA-122 is associated with the pathogenesis of many cardiovascular diseases, including apoptosis and was found highly increased in our previous rat model of post-myocardial infarction heart failure. In this study, we aimed to identify the target gene of microRNA-122 and to evaluate their impacts on the protective effect of acylated ghrelin in angiotensin II-induced apoptosis. The results showed that microRNA-122 was upregulated in the angiotensin II administration group accompanied by increased cell apoptosis, which were both reversed by ghrelin. Furthermore, microRNA-122 mimics upregulated numerous pro-apoptotic genes and increased apoptosis. The luciferase activity assay revealed Sestrin-2 as a direct target of microRNA-122.The expression of Sestrin-2 was downregulated by angiotensin II and upregulated by co-treatment with ghrelin. Inhibition of microRNA-122 and overexpression of Sestrin-2 alleviated apoptosis which was further reduced upon administered of ghrelin. Together, these results indicated that Sestrin-2 expression is inhibited by microRNA-122 and that this inhibition is involved in the protective effect of ghrelin and angiotensin II-induced apoptosis. We also found that microRNA-122 influenced several apoptosis pathways including the caspase cascade reaction and death receptor-mediated pathways. Collectively, our data reveal that microRNA-122 and its target gene Sestrin-2, under the regulation of angiotensin II and ghrelin, are important players in cardiomyocyte apoptosis. We therefore believe that microRNA-122 and Sestrin-2 can be developed as potential therapeutic targets against apoptosis in cardiovascular diseases.

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Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction

Cited by 86 publications

References 38 publications

Bone marrow-derived mesenchymal stem cells overexpressing miR-21 efficiently repair myocardial damage in rats

Bone marrow-derived mesenchymal stem cells overexpressing miR-21 efficiently repair myocardial damage in rats

Molecular miR-19a in Acute Myocardial Infarction: Novel Potential Indicators of Prognosis and Early Diagnosis

The impact of microRNA-122 and its target gene Sestrin-2 on the protective effect of ghrelin in angiotensin II-induced cardiomyocyte apoptosis

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