Overexpression of miR-24 Is Involved in the Formation of Hypocoagulation State after Severe Trauma by Inhibiting the Synthesis of Coagulation Factor X

Abstract

Background: Dysregulation of microRNAs may contribute to the progression of trauma-induced coagulopathy (TIC). We aimed to explore the biological function that miRNA-24-3p (miR-24) might have in coagulation factor deficiency after major trauma and TIC.

Methods: 15 healthy volunteers and 36 severe trauma patients (Injury Severity Score ≥ 16 were enrolled. TIC was determined as the initial international normalized ratio >1.5. The miR-24 expression and concentrations of factor X (FX) and factor XII in plasma were measured. In vitro study was conducted on L02 cell line.

Results: The plasma miR-24 expression was significantly elevated by 3.17-fold (P = 0.043) in major trauma patients and reduced after 3 days (P < 0.01). The expression level was significantly higher in TIC than in non-TIC patients (P = 0.040). Multivariate analysis showed that the higher miR-24 expression was associated with TIC. The plasma concentration of FX in TIC patients was significantly lower than in the non-TIC ones (P = 0.030) and controls (P < 0.01). A negative correlation was observed between miR-24 and FX. miR-24 transduction significantly reduced the FX level in the supernatant of L02 cells (P = 0.030).

Conclusions: miR-24 was overexpressed in major trauma and TIC patients. The negative correlation of miR-24 with FX suggested the possibility that miR-24 might inhibit the synthesis of FX during TIC.

Figure 1

(a) Comparison of plasma expression levels of miR-24 in 36 major trauma patients and 15 controls. Plasma expression levels of miR-24 were higher in all major trauma patients than in healthy controls. ^∗P < 0.05. (b) Plasma expression levels of miR-24 were significantly increased in 8 TIC patients than in the 28 non-TIC ones on ED arrival. MiR-24 expression levels were significantly downregulated on day 3 compared with those on day 0 (n = 24 in the non-TIC day-3 group and n = 7 TIC day 3 group). Compared to the non-TIC day 0 group, ^∗P < 0.05, ^∗∗P < 0.01, compared to the TIC day 0 group, ^#P < 0.01.

Figure 2

(a) The average level of FX in 8 TIC patients was significantly lower than that in 15 controls and 28 non-TIC patients. (b) Reduction in the average level of FXII in TIC patients compared to that in healthy controls was also noted. ^∗P < 0.05, ^∗∗P < 0.01.

Figure 3

Correlation analysis for miR-24 expression and the level of FX (n = 36).