The microRNA-144/451 cluster in plasma-derived microvesicles and erythrocytes in patients with history of pulmonary embolism

Abstract

Chronic thromboembolic disease (CTED) and chronic thromboembolic pulmonary hypertension (CTEPH) are the complications that comprise a serious problem for patients with history of pulmonary embolism (PE). Erythrocytes, extracellular microvesicles (EMVs) and miRNAs play a substantial role in the procoagulant states. The aim. To analyze the levels of miR-144-3р, miR-451a, and miR-451b in blood plasma-derived EMVs and erythrocytes in patients with history of PE and in the control group. Materials and Methods. 18 patients with history of PE (13 CTEPH, 5 CTED) and 8 controls were enrolled into the study. All the participants had undergone clinical and biochemical blood tests as well as the coagulogram. We used flow cytometry to assess plasma-derived EMVs (CD9, CD41, CD45, CD235a, CD105). We measured the expression of miR-144-3р, miR-451a, miR-451b by real-time PCR with endogenous control (miR-152-3p) and five exogenous quality controls. Results. The levels of miR-144-3р and miR-451a in patients were lower than in controls, both in EMVs (р = 0.030; р = 0.065) and in erythrocytes (р = 0.023;р = 0.086). In female patients, the levels of miR-144-3р and miR-451a in CTEPH were lower than in CTED (р = 0.087; р = 0.031). Mir-451b in EMVs has not been detected, while in erythrocytes its levels have not differed between the groups. In patients, the levels of miR-144-3р and miR-451a directly correlated with each other both in EMVs (р = 0.004) and in erythrocytes (р = 0.042). In all the participants, the levels of miR-144-3р and miR-451a in EMVs directly correlated with those in erythrocytes (р = 0.002; р = 0.078). The number of erythrocyte-derived EMVs correlated with miR-451a levels both in EMVs (R = 0.472; p = 0.065) and in erythrocytes (R = –0.829; p = 0.011). The level of miR-451a in EMVs correlated with blood plasma levels of factor VIII and fibrinogen (R = 0.584; p = 0.022 and R= –0.489; p = 0.047), and with the International Normalized Ratio (R = 0.894; p = 0.041). Conclusion. The microRNA-144/451 cluster may influence both the hemostasis system and the risk of post-thromboembolic complications development. In the present study, miR-144-3р and miR-451a showed themselves as protective factors in relation to both the development of PE and severity of post-thromboembolic complications.