Role of microRNAs in Venous Thromboembolism

Abstract

MicroRNAs (miRNAs) are non-coding RNAs that execute their function by targeted downregulation of gene expressions. There is growing evidence from epidemiological studies and animal models suggesting that the expression level of miRNAs is dysregulated in venous thromboembolism (VTE). In this review, we summarize the current knowledge on the role of miRNAs as biomarkers for VTE and provide general insight into research exploring the modulation of miRNA activity in animal models of venous thrombosis. Up to now, published studies have yielded inconsistent results on the role of miRNAs as biomarkers for VTE with most of the reports focused on diagnostic research. The limited statistical power of the individual studies, due to the small sample sizes, may substantially contribute to the poor reproducibility among studies. In animal models, over-expression or inhibition of some miRNAs appear to influence venous thrombus formation and resolution. However, there is an important gap in knowledge on the potential role of miRNAs as therapeutic targets in VTE. Future research involving large cohorts should be designed to clarify the clinical usefulness of miRNAs as biomarkers for VTE, and animal model studies should be pursued to unravel the role of miRNAs in the pathogenesis of VTE and their potential as therapeutic targets.

Keywords: animal model; biomarker; microRNAs; venous thromboembolism; venous thrombosis.

Figure 1

A simplified overview of blood coagulation and fibrinolysis pathways and the microRNAs (miRNAs) reported to regulate key hemostatic factors (see Table 1 for literature references). Black arrow indicates activation of hemostatic factors. AT, antithrombin; FDPs, fibrin degradation products; PC, protein C; PS, protein S; PAI-1, plasminogen activator inhibitor-1; TFPI, tissue factor pathway inhibitor; tPA, tissue plasminogen activator; uPA, urokinase plasminogen activator.