Role of microRNAs in Venous Thromboembolism

Morelli, Vânia M.; Brækkan, Sigrid Kufaas; Hansen, John‐Bjarne

doi:10.3390/ijms21072602

Cited by 30 publications

(26 citation statements)

References 73 publications

(130 reference statements)

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“…As Morelli et al recently argued, clarifying this issue could be worthy, not only for the potential clinical use of miRNAs as predictive biomarkers for VTE but also as targets for novel therapeutics approaches. 32 In animal studies, two models have been mostly proposed: the occlusive one (stasis model) and the non-occlusive one (stenosis model); many miRNA were identified to increase homing of endothelial progenitor cells and venous thrombus resolution in experimental DVT, 38,43 supporting that miRNAs act on genes implicated in the regulation of cell differentiation, migration, apoptosis, and angiogenesis.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

“…According to our literature review, many heterogeneous studies have evaluated the role of miRNAs in VTE: epidemiological reports (case-control studies), in vivo studies in animal models of venous thrombosis, and in vitro studies correlating miRNA to direct molecular targets. 32 The number of studies exploring the role of miRNAs as VTE biomarkers has substantially increased during the past few years. However, most of the epidemiological reports were case-control studies evaluating miRNAs as potential diagnostic biomarkers of VTE.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

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MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study

Rossetti

Goldoni

Pengo

et al. 2021

Semin Thromb Hemost

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Venous thromboembolism (VTE) is the third most common cardiovascular disease. Interleukins (ILs) and micro-ribonucleic acids (miRNAs) have been proposed as molecules able to modulate endothelial inflammation and platelet hyperactivity. At present, no early biomarkers are available to predict the outcome of VTE. We investigated in a pilot study a selected number of miRNAs and ILs as prognostic VTE biomarkers and reviewed literature in this setting. Twenty-three patients (aged 18–65) with a new diagnosis of non-oncological VTE and free from chronic inflammatory diseases were enrolled. Twenty-three age- and sex-matched healthy blood donors were evaluated as control subjects. Serum miRNAs (MiRNA 126, 155, 17.92, 195), inflammatory cytokines (IL-6, tumor necrosis factor-α, IL-8), and lymphocyte subsets were evaluated in patients at enrolment (T0) and in controls. In VTE patients, clinical and instrumental follow-up were performed assessing residual vein obstruction, miRNA and ILs evaluation at 3 months' follow-up (T1). At T0, IL-8, activated T lymphocytes, Treg lymphocytes, and monocytes were higher in patients compared with healthy controls, as were miRNA 126 levels. Moreover, miRNA 126 and IL-6 were significantly increased at T0 compared with T1 evaluation in VTE patients. Higher levels of MiR126 at T0 correlated with a significant overall thrombotic residual at follow-up. In recent years an increasing number of studies (case–control studies, in vivo studies in animal models, in vitro studies) have suggested the potential role of miRNAs in modulating the cellular and biohumoral responses involved in VTE. In the frame of epidemiological evidence, this pilot study with a novel observational approach supports the notion that miRNA can be diagnostic biomarkers of VTE and first identifies miRNA 126 as a predictor of outcome, being associated with poor early recanalization.

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Section: Discussion and Literature Reviewmentioning

confidence: 99%

Section: Discussion and Literature Reviewmentioning

confidence: 99%

MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study

Rossetti

Goldoni

Pengo

et al. 2021

Semin Thromb Hemost

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“…In addition, miR-532 18 and miR-320a/b 19 have been found to be up-regulated in DVT patients, which are the potential biomarkers for improving the diagnostic accuracy of DVT. Some serum miRNAs have been considered as the potential biomarkers for the diagnosis of VTE 17 , 20 – 23 . In this study, the levels of miR-124-3p and miR-506-3p were significantly higher in sick group than those in the healthy group, which were related to the decline of PROC protein and PROC mRNA.…”

Section: Discussionmentioning

confidence: 99%

MiR-124 and miR-506 are involved in the decline of protein C in children with extra-hepatic portal vein obstruction

Zhang

Long

2021

Sci Rep

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The deficiency of protein C (PROC) can be partly rescued by Rex shunt through restoring portal blood flow in children with extra-hepatic portal venous obstruction (EHPVO). However, the decline of PROC is still found in some patients with a normal portal blood flow after Rex shunt. The aim of this study was to identify the candidate miRNAs involving in the decline of PROC and their mechanism. The protein level of PROC was detected by the ELISA assay, and was compared between sick and healthy groups. The expressions of miRNAs and PROC mRNA were measured using qRT-PCR, and were compared between sick and healthy groups. The correlation between PROC and candidate miRNAs was analysed by a Pearson correlation analysis to identify the most significant miRNAs. The expression of PROC mRNA was detected by qRT-PCR in HL-7702 and LX-2 cells tansfected with miRNAs mimics or inhibitors and negative control (NC) mimics, which was compared among the different groups. The rates of liver cells’ proliferation and apoptosis were detected in HL-7702 and LX-2 cells tansfected with miRNAs mimics or inhibitors or with overexpressing PROC and negative control mimics by CKK8 assay and flow cytometry, which were compared among the different groups. The expressions of COX-2 and VEGF were measured by qRT-PCR, and were compared between the miRNAs groups and NC group. Western blot was assayed for detecting the protein levels of PROC, COX-2, VEGF, Bcl-2 and Bax, which were compared between the miRNAs groups and NC group. The expression of PROC mRNA was lower, and the expressions of miR-506-3p and miR-124-3p were higher in children with EHPVO than healthy group. PROC mRNA was negatively correlated with the expression of miR-506-3p and miR-124-3p. Compared to the NC group, the transcription activity of PROC was lower after exposure of miR-506 and miR-124 mimics in HL-7702 and LX-2 cells, but this phenomenon was reversed after inhibiting miR-506 and miR-124. The rate of cell proliferation was lower after exposure of miR-506 and miR-124 than the NC group, which was increased after inhibiting miR-506 and miR-124 in HL-7702 cells and overexpressing PROC in LX-2 cells. The apoptotic rate was higher after exposure of miR-506 and miR-124 than the NC group, which was decreased after inhibiting miR-506 and miR-124 in HL-7702 cells and overexpressing PROC in LX-2 cells. The mRNA levels of COX-2 and VEGF were significantly higher after exposure of miR-506 and miR-124 mimics than those in the NC group. The protein levels of PROC and Bcl-2 were down-regulated, and the levels of COX-2, Bax and VEGF were up-regulated after exposure of miR-506 and miR-124 in HL-7702 cells, but this phenomenon was reversed after inhibiting miR-506 and miR-124. MiR-506-3p and miR-124-3p may involve in the decline of PROC in protein and transcriptional level, in which the anti-proliferation and pro-apoptosis role of miR-506-3p and miR-124-3p for liver cells may involve in this mechanism.

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“…Several lines of evidence implicate significant functional roles for miRNAs in the regulation of the hemostatic system. Firstly, a growing number of studies show essential contributions of miRNAs to the regulation of hemostatic (De Los Reyes-Garcia, et al, 2019;Teruel-Montoya, Rosendaal, & Martinez, 2015) and thrombotic (Arroyo, et al, 2018;Hembrom, Srivastava, Garg, & Kumar, 2020;Morelli, Braekkan, & Hansen, 2020) functions (Table 3). Secondly, miRNAs have been demonstrated to directly regulate multiple hemostatic factors through interactions with the 3'UTR.…”

Section: Evidence For a Functional Role Of Mirnas In The Hemostatic Smentioning

confidence: 99%

A novel rationale for targeting FXI: Insights from the hemostatic miRNA targetome for emerging anticoagulant strategies

Nourse

Danckwardt

2018

Preprint

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The treatment and prevention of thrombosis is currently under a period of rapid change with the replacement of traditional anticoagulant vitamin K antagonists with direct oral anticoagulants (DOACs), which specifically target factors FXa or FIIa.Nevertheless therapeutic targeting of blood coagulation is an inherently difficult task as it interferes with the delicate balance of pro-and anticoagulant activities. Although anticoagulants are employed in millions of thrombophilic patients worldwide each year, for a growing population with comorbidities who exhibit an increased risk of bleeding with DOAC treatment satisfying therapeutic options are still lacking and the quest for novel therapeutics continues.Recently the targeting of factors FXI and FXII have emerged as new therapeutic strategies. As these factors play an important roles in thrombosis, however are more or less functionally dispensable for hemostasis, they may potentially overcoming the functional obstacle of treating or preventing thrombosis without affecting hemostasis.A key question in following up this approach is which of these two factors is likely to be the more reliable target? Here we present and discuss a hitherto unrecognized rationale for the therapeutic targeting of FXI. This is based on mimicking endogenous FXI gene expression control by therapeutic delivery of miRNA mimics.Studies are urgently needed to test this therapeutic principle in a clinical setting. This is particularly applicable in hemostaseology where monitoring of therapeutic effects remains a daily routine and thus assessment of the efficacy and safety of such therapeutic components could be simply implemented ushering in a novel therapeutic era with broad applicability.

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Role of microRNAs in Venous Thromboembolism

Cited by 30 publications

References 73 publications

MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study

MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study

MiR-124 and miR-506 are involved in the decline of protein C in children with extra-hepatic portal vein obstruction

A novel rationale for targeting FXI: Insights from the hemostatic miRNA targetome for emerging anticoagulant strategies

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