Abstract
We investigated whether stable eukaryotic translation initiation factor 3e/inter 6 (eIF-3e/Int6) RNA-silencing (siRNA-Int6) can ameliorate pre-eclampsia (PE) by promoting angiogenesis in an N-nitro-L-arginine methyl ester (L-NAME)-induced rat pre-eclampsia (PE) model. Twenty-four pregnant female Sprague–Dawley rats were allocated into 4 groups, including controls (Con) without any treatment, and 18 from gestational day (GD) 7 to GD17 L-NAME-treated rats, which were divided into stable siRNA-Int6 transfected (siRNA-Int6), negative vector control siRNA (NC-siRNA) and PE control (PE-Con) groups. All adenovirus siRNA transfections were performed on GD7 via intravenous tail injection. On GD0, GD11 and GD17, blood pressure, and on GD6 and GD17, protein estimations in 24 h urine samples were conducted. All animals were sacrificed on GD18. In the PE-Con group, placental Int6 was expressed to a significantly greater level than in the Con group, which was reversed by the application of siRNA-Int6. Blood pressure and proteinuria were significantly lower in the siRNA-Int6 group than in the PRE-Con group. As shown by CD31 and IB4 expression, placental micro-vascular density (MVD) was significantly higher in the siRNA-Int6 group than in the PE-Con and NC-siRNA groups, which has accompanied by enhanced trophoblast invasion. Int6 silencing alleviated the maternal clinical manifestations of pre-eclampsia and promoted placental angiogenesis in pregnant L-NAME-treated rats.
Highlights
In the serum of PE control (PE-Con) rats the concentrations of IL-6 and IL-8 were significantly decreased compared to the Con group (Fig. 4a,b), which was significantly restored by siRNA-int[6] for IL-6, whereas Int-6 silencing had no effect on basic fibroblast growth factor (bFGF) serum concentrations (Fig. 4c)
On GD11, compared with the Con group (118.13 ± 5.93 mmHg) the systolic blood pressure (SBP) was significantly increased in the PE-Con group (140.78 ± 5.79 mmHg) (P < 0.001) and the vector control group (141.27 ± 9.11 mmHg) (P < 0.001) as well as in the siRNA-Int[6] group (129.88 ± 5.89 mmHg), but to a smaller extent (P < 0.05)
On GD17, the SBP was again significantly higher in the PE-Con (147.85 ± 7.61 mmHg) and the NC-siRNA (146.83 ± 9.14 mmHg) groups compared with the Con group (116.75 ± 5.55 mmHg) (P < 0.001)
Summary
In the siRNA-Int[6] group, the apparent enhancement of serum HIF2α concentrations did not reach statistical significance (Fig. 3b). The SBP was not significantly different between the Con (116.75 ± 5.55 mmHg) and the siRNA-Int[6] groups (125.33 ± 7.03 mmHg) (P > 0.05) at that time (Fig. 5a).
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