MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review

Czajka, Pamela; Fitas, Alex; Jakubik, Daniel; Eyileten, Ceren; Wicik, Zofia; Siller‐Matula, Jolanta M.; Postuła, Marek

doi:10.3389/fphys.2021.652579

Cited by 34 publications

(40 citation statements)

References 133 publications

(198 reference statements)

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“…Although we cannot exclude the possibility that this could be partly because of platelet contamination or lysis, among a list of 11 miRNAs previously reported to strongly correlate with platelet contamination (Mitchell et al, 2016) only two (hsa-miR-93-5p and hsa-miR-17-5p) correlated with platelets in more than one severity group in our study. Alternatively, as platelet-secreted miRNAs reflect platelet activation and function (Czajka et al, 2021), severity group-specific platelet-associated miRNA signatures could provide novel insight into the observed thrombocytopenia and platelet aggregation phenotype in severe COVID-19 (Lippi et al, 2020;Rampotas and Pavord, 2020).…”

Section: Ll Open Access Isciencementioning

confidence: 99%

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

et al. 2022

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Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalised COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g. IL6, CCL20) or clinical hallmarks of COVID-19 (e.g. neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Analysis of an independent cohort of 108 patients from a different centre (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover hospital blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19.

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Section: Ll Open Access Isciencementioning

confidence: 99%

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

et al. 2022

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“…Platelets are found to be a significant source of miRNAs, small (18–25 nucleotides), non-coding RNAs, that influence various aspects of cellular functions through the regulation of gene expression. A single miRNA can influence the expression of multiple genes, and one single target can be regulated by several miRNAs [ 9 , 10 ]. Circulating miRNAs can be detected in many body fluids including plasma, serum, or whole blood, and they are stable in biological samples.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, they can be used as diagnostic and prognostic novel biomarkers as well as novel therapeutic targets [ 11 , 12 ]. Due to the number of limitations of currently used platelet function tests, circulating miRNAs could be promising biomarkers of inflammation and platelet function and were previously described to participate in processes of platelet activation and aggregation [ 9 , 13 ]. Alteration in their expression is associated with various biological processes, including platelet reactivity, glucose metabolism, antiplatelet drug response, and anti-inflammatory response [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study

Eyileten

Wicik

Keshwani

et al. 2022

Cardiovasc Diabetol

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Background In patients with type 2 diabetes mellitus (T2DM) an association between severe hypoglycaemic episodes and the risk of cardiovascular (CV) morbidity and mortality has been previously established. Methods We aimed to investigate the influence of hypoglycaemia on several diabetes-related and platelet-related miRNAs selected based on bioinformatic analysis and literature search, including hsa-miR-16, hsa-miR-34a, hsa-miR-129-2, hsa-miR-15a, hsa-miR-15b, hsa-miR-106a, miR-223, miR-126. Selected miRNAs were validated by qRT-PCR in 14 patients with T2DM on metformin monotherapy, without established CV disease and antiplatelet therapy during a stepwise hypoglycaemic clamp experiment and a follow-up 7 days after the clamp event. In order to identify which pathways and phenotypes are associated with validated miRNAs we performed target prediction on genes expressed with high confidence in platelets. Results Circulating levels of miR-106a-5p, miR-15b, miR-15a, miR-16-5p, miR-223 and miR-126 were increased after euglycaemic clamp followed by hypoglycaemic clamp, each with its distinctive time trend. On the contrary, miR-129-2-3p, miR-92a-3p and miR-34a-3p remained unchanged. MiR-16-5p was negatively correlated with interleukin (IL)-6, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) (p = 0.002, p < 0.001, p = 0.016, respectively), whereas miR-126 was positively correlated with VCAM (p < 0.001). There were negative correlations between miR-16-5p, miR-126 and coagulation factors, including factor VIII and von Willebrand factor (vWF). Among all studied miRNAs, miR-126, miR-129-2-3p and miR-15b showed correlation with platelet function. Bioinformatic analysis of platelet-related targets of analyzed miRNAs showed strong enrichment of IL-2 signaling. We also observed significant enrichment of pathways and diseases related to cancer, CV diseases, hyperglycemia, and neurological diseases. Conclusions Hypoglycaemia can significantly influence the expression of platelet-enriched miRNAs, with a time trend paralleling the time course of platelet activation. This suggests miRNAs could be exploited as biomarkers for platelet activation in response to hypoglycaemia, as they are probably released by platelets upon activation by hypoglycaemic episodes. Should they hold their promise in clinical endpoint studies, platelet-derived miRNAs might become helpful markers of CV risk in subjects with diabetes. Trial registration The study was registered at clinical trials.gov; Impact of Hypoglycaemia in Patients With DIAbetes Mellitus Type 2 on PLATElet Activation (Diaplate), trial number: NCT03460899

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“…It was reported that blood platelets express a vast amount of miRNAs that control their functions and reactivity [ 12 ]. Moreover, platelets contain all necessary protein enzymes delivered from megakaryocytes to convert pre-miRNA to mature sequences [ 13 ], thus constituting an excellent area for miRNA evaluation.…”

Section: Introductionmentioning

confidence: 99%

Screening Analysis of Platelet miRNA Profile Revealed miR-142-3p as a Potential Biomarker in Modeling the Risk of Acute Coronary Syndrome

Szelenberger

Karbownik

Kacprzak

et al. 2021

Cells

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Transcriptome analysis constitutes one of the major methods of elucidation of the genetic basis underlying the pathogenesis of various diseases. The post-transcriptional regulation of gene expression is mainly provided by microRNAs. Their remarkable stability in biological fluids and their high sensitivity to disease alteration indicates their potential role as biomarkers. Given the high mortality and morbidity of cardiovascular diseases, novel predictive biomarkers are sorely needed. Our study focuses for the first time on assessing potential biomarkers of acute coronary syndrome (ACS) based on the microRNA profiles of platelets. The study showed the overexpression of eight platelet microRNAs in ACS (miR-142-3p; miR-107; miR-338-3p, miR-223-3p, miR-21-5p, miR-130b-3p, miR-301a-3p, miR-221-3p) associated with platelet reactivity and functionality. Our results show that the combined model based on miR-142-3p and aspartate transaminase reached 82% sensitivity and 88% specificity in the differentiation of the studied groups. Furthermore, the analyzed miRNAs were shown to cluster into two orthogonal groups, regulated by two different biological factors. Bioinformatic analysis demonstrated that one group of microRNAs may be associated with the physiological processes of platelets, whereas the other group may be linked to platelet–vascular environment interactions. This analysis paves the way towards a better understanding of the role of platelet microRNAs in ACS pathophysiology and better modeling of the risk of ACS.

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MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review

Cited by 34 publications

References 133 publications

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study

Screening Analysis of Platelet miRNA Profile Revealed miR-142-3p as a Potential Biomarker in Modeling the Risk of Acute Coronary Syndrome

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