Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction

Jakob, Philipp; Kacprowski, Tim; Briand-Schumacher, Sylvie; Heg, Dik; Klingenberg, Roland; Stähli, Barbara E.; Jaguszewski, Miłosz; Rodondi, Nicolas; Nanchen, David; Räber, Lorenz; Vogt, Pierre; Mach, François; Windecker, Stephan; Völker, Uwe; Matter, Christian M.; Lüscher, Thomas F.; Landmesser, Ulf

doi:10.1093/eurheartj/ehw563

Cited by 70 publications

(64 citation statements)

References 16 publications

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“…Both miR-320 and miR-140 are elevated in human with heart failure [32]. miR-320a was identified as a marker to discriminate between patients experiencing and those not experiencing major adverse cardiovascular events within the first year after ST-segment-elevation myocardial infarction [33]. miR-320a was significantly upregulated in heart failure myocardium compared to normal controls [34].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Circulating miRNAs could serve as biomarkers for diagnosis or prognosis of heart diseases and cerebrovascular diseases. Dexmedetomidine has protective effects in various organs. The effects of dexmedetomidine on circulating miRNAs remain unknown. Here, we investigated differentially expressed miRNA and to predict the target genes of the miRNA in patients receiving dexmedetomidine. Methods: The expression levels of circulating miRNAs of 3 patients were determined through high through-put miRNA sequencing technology. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 7.1 and miRDB v.5. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional annotation and pathway enrichment analysis of target genes respectively. Results: Twelve differentially expressed miRNAs were identified. Five miRNAs were upregulated (hsa-miR-4508, hsa-miR-novel-chr8_87373, hsa-miR-30a-3p, hsa-miR-novel-chr16_26099, hsa-miR-4306) and seven miRNAs (hsa-miR-744-5p, hsa-miR-320a, hsa-miR-novel-chr9_90035, hsa-miR-101-3p, hsa-miR-150-5p, hsa-miR-342-3p, and hsa-miR-140-3p) were downregulated after administration of dexmedetomidine in the subjects. The target genes and pathways related to the differentially expressed miRNAs were predicted and analyzed. Conclusion: The differentially expressed miRNAs may be involved in the mechanisms of action of dexmedetomidine. Specific miRNAs, such as hsa-miR-101-3p, hsa-miR-150-5p and hsa-miR-140-3p, are new potential targets for further functional studies of dexmedetomidine.

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Section: Discussionmentioning

confidence: 99%

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Yang

Chen

et al. 2018

Cell Physiol Biochem

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“…For example, miR-21 is associated with organ fibrosis and the measurement may be useful in the detection of renal or myocardial fibrosis (93, 94). Several studies have started to clarify the prognostic roles of various miRNAs in large cohorts (95). However, available data are limited especially in the context of CRS, and more studies and validation in large cohorts are necessary for establishing the clinical utility of circulating and urinary miRNAs.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Renocardiovascular Biomarkers: from the Perspective of Managing Chronic Kidney Disease and Cardiovascular Disease

Niizuma

Iwanaga

Yahata³

et al. 2017

Front. Cardiovasc. Med.

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Mortality among the patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains high because of the very high incidence of cardiovascular disease (CVD) such as coronary artery disease, cardiac hypertrophy, and heart failure. Identifying CVD in patients with CKD/ESRD remains a significant hurdle and the early diagnosis and therapy for CVD is crucial in these patients. Therefore, it is necessary for the better management to identify and utilize cardiovascular (CV) biomarkers in profiling CVD risk and enabling stratification of early mortality. This review summarizes current evidence about renocardiovascular biomarkers: CV biomarkers in patients with CKD as well as with ESRD, emphasizing on the emerging biomarkers: B-type natriuretic peptide, cardiac troponins, copeptin, the biomarker of renal injury (neutrophil gelatinase-associated lipocalin), and the mineral and bone disorder hormone/marker (fibroblast growth factor-23). Furthermore, it discusses their potential roles especially in ESRD and in future diagnostic and therapeutic strategies for CVD in the context of managing cardiorenal syndrome.

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“…Thus, platelet activation can change miRNA expression profiles , although this is not shown in all studies . Moreover, miRNA profiles are changed in patients with myocardial infarction , and platelet miRNAs are differentially expressed in hyperreactive and hyporeactive subjects . In the present study, we sought to illustrate the impacts of platelet miRNAs on platelet function.…”

Section: Discussionmentioning

confidence: 90%

“…Platelets contain a number of miRNAs and are equipped with fully functional miRNA effector complexes, namely Dicer and Ago2 . During the recent years, there have been continuous efforts to investigate the biomarker potentials of circulating miRNAs for platelet dysfunction and/or cardiovascular diseases . Thus, platelet activation can change miRNA expression profiles , although this is not shown in all studies .…”

Section: Discussionmentioning

confidence: 99%

Thrombin‐reduced miR‐27b attenuates platelet angiogenic activities in vitro via enhancing platelet synthesis of anti‐angiogenic thrombospondin‐1

Miao

Rahman

Jiang

et al. 2018

Journal of Thrombosis and Haemostasis

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Background Platelets can synthesize proteins upon activation. Platelets contain a number of microRNAs (miRNA) and a fully functional miRNA effector machinery. It is, however, unclear if platelet miRNAs can regulate protein synthesis of platelets, and whether the regulation may produce a physiological impact. Objectives To investigate if and how platelet miRNAs regulate de novo syntheses of angiogenic regulators and subsequently modulate platelet angiogenic activities. Methods and Results Microarray-based miRNA profiling showed that thrombin stimulation in vitro down- or up-regulated a number of platelet miRNAs, both in the total platelet miRNAs and in Ago2-associated miRNAs. Among those altered miRNAs, miR-27b was down-regulated in both the total and Ago2-immunoprecipitated miRNA profiles of platelets, which was confirmed by reverse transcription-quantitative PCR (RT-qPCR). Using western blotting assays, we showed that thrombin induced platelet de novo synthesis of thrombospondin-1, and that the level of thrombospondin-1 synthesis could reach a level of 3-5-fold higher than that before thrombin stimulation. With either the platelet precursor megakaryocyte cell line MEG-01 cells or mature platelets, we demonstrated that transfection of miR-27b mimic, but not the negative control of miRNA mimic, markedly reduced thrombospondin-1 protein levels. The latter subsequently enhanced platelet-dependent endothelial tube formation on matrigel. Conclusions Thrombin stimulation in vitro reduces platelet miR-27b levels that may markedly enhance thrombin-evoked platelet de novo synthesis of thrombospondin-1. Elevation of platelet miR-27b by transfection inhibits thrombospondin-1 synthesis, and subsequently enhances platelet pro-angiogenic activities. Hence, platelet activation-dependent reduction of miR-27b levels may represent a novel negative regulatory mechanism of platelet angiogenic activities.

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Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction

Cited by 70 publications

References 16 publications

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Circulating miRNA Expression Profiling and Target Prediction in Patients Receiving Dexmedetomidine

Renocardiovascular Biomarkers: from the Perspective of Managing Chronic Kidney Disease and Cardiovascular Disease

Thrombin‐reduced miR‐27b attenuates platelet angiogenic activities in vitro via enhancing platelet synthesis of anti‐angiogenic thrombospondin‐1

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