Long Non-Coding RNAs in Venous Thromboembolism: Where Do We Stand?

Abstract

Venous thromboembolism (VTE), a common condition in Western countries, is a cardiovascular disorder that arises due to haemostatic irregularities, which lead to thrombus generation inside veins. Even with successful treatment, the resulting disease spectrum of complications considerably affects the patient’s quality of life, potentially leading to death. Cumulative data indicate that long non-coding RNAs (lncRNAs) may have a role in VTE pathogenesis. However, the clinical usefulness of these RNAs as biomarkers and potential therapeutic targets for VTE management is yet unclear. Thus, this article reviewed the emerging evidence on lncRNAs associated with VTE and with the activity of the coagulation system, which has a central role in disease pathogenesis. Until now, ten lncRNAs have been implicated in VTE pathogenesis, among which MALAT1 is the one with more evidence. Meanwhile, five lncRNAs have been reported to affect the expression of TFPI2, an important anticoagulant protein, but none with a described role in VTE development. More investigation in this field is needed as lncRNAs may help dissect VTE pathways, aiding in disease prediction, prevention and treatment.

Long Non-Coding RNAs: Bridging Cancer-Associated Thrombosis and Clinical Outcome of Ovarian Cancer Patients

“…Subsequently, in recent years, multiple lncRNAs have been implicated in venous thrombus formation and resolution. However, the data on cancer patients are scarce [ 18 ]. Thus, this study evaluated the impact of VTE-associated lncRNAs on the incidence of OC-related VTE and their prognostic value among OC patients.…”

“…Regarding the evaluated lncRNAs, starting with MALAT1, it has been pointed out as a major player in thrombogenesis due to its downregulation in atherosclerotic plaques and its association with endothelial function [ 41 , 42 ]. Inconsistent results, however, led to the hypothesis that this lncRNA may have a cell- and/or context-dependent role in VTE [ 18 , 42 , 43 , 44 ]. In the present study, higher pre-chemotherapy expression levels of MALAT1 in PBCs, irrespective of the first treatment (surgery vs. chemotherapy), were associated with higher leukocyte (profile A, Χ 2 , p = 0.041) and neutrophil (profile A, Χ 2 , p = 0.041) counts.…”

“…In contrast with the other evaluated lncRNAs, MEG8 has not yet been directly linked to VTE in previous studies. Instead, it is reported to be a scaffold lncRNA repressing the expression of tissue factor pathway inhibitor 2 (TFPI2) [ 18 , 85 ]. This haemostatic protein is expressed in cells such as monocytes or macrophages and endothelial cells, playing dual roles: as an anticoagulant by targeting the extrinsic coagulation pathway (also known as the TF coagulation pathway) and as an anti-fibrinolytic protein by inhibiting plasmin.…”

“…Given the roles of the tumour coagulome in cancer growth and progression, it is important to identify biomarkers of OC-related VTE as they might improve the management of both VTE and OC [ 17 ]. Recently, multiple long non-coding RNAs (lncRNAs) were shown to influence venous thrombus formation and resolution; however, the data specifically among cancer patients are scarce [ 18 ]. Given the impact of platelets, endothelial cells and leukocytes on both thrombogenesis and tumour progression, as well as the high incidence and negative effect of VTE among OC patients, VTE-associated lncRNAs may influence the pathogenesis of OC-related VTE and constitute valuable OC prognostic biomarkers regardless of VTE.…”

Contribution of Endothelial Dysfunction to Cancer Susceptibility and Progression: A Comprehensive Narrative Review on the Genetic Risk Component

“…Venous thromboembolism (VTE), also referred to as venous thrombosis, is a prevalent and intricate cardiovascular condition. The disease has two main manifestations: when the thrombus first forms in a deep vein-deep vein thrombosis (DVT)-followed by its migration into the bloodstream and subsequent lodging in the lungs-pulmonary embolism (PE) [1]. In Europe, VTE affects around one to two individuals per 1000 annually [2].…”