Acute effect of statins on vascular reactivity in maternal and placental arteries from pregnancies complicated by preeclampsia

Figures

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  FIGURE 1. Assessment of vascular reactivity in OAs from normal and PE pregnancies. Assessment of U46619-induced contraction expressed as tension (A) or as %KPSS (B). Relaxation to bradykinin post-incubation (C). Compared to the endothelial function pre-incubation, there was a significant change in endothelial function between the NP and PE groups after relaxation with bradykinin (D). Replicate vessels from the same pregnancy were averaged for each sample. Graphs A and B show the combined pre-incubation U46619 data for normal pregnancy (N = 34) from the pitavastatin (N = 18) and pravastatin (N = 16) experiments. Data are expressed as mean ± SEM; two-way ANOVA (A–C) and as median, IQR with Mann–Whitney test for graph (D).

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  FIGURE 2. Effect of 2-h incubation with 1 µM pitavastatin on the contraction of OAs from normal pregnancies. Assessment of U46619-induced contraction expressed as tension (kPa) in normal pregnancy (A) and PE pregnancy (B). There was no significant effect on the contraction of OAs. U46619 dose–response curves were compared using two-way ANOVA. Data are expressed as mean ± SEM; number of omental biopsies in parentheses.

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  FIGURE 3. Effect of 2-h statin incubation on relaxation of OAs from normal pregnancies. Following a 2-hr incubation with pitavastatin at 1 µM, there was no significant effect on relaxation of OAs to BK in vessels from normal pregnancies (A) or from PE pregnancies (B). BK dose–response curves were compared using two-way ANOVA. Data are expressed as mean ± SEM; number of omental biopsies in parentheses.

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  FIGURE 4. Assessment of vascular reactivity in CPAs from normal and PE pregnancies. Assessment of U46619-induced contraction expressed as tension (A) or as %KPSS (B). Relaxation to SNP (C). There was no significant difference between CPAs from normal versus PE pregnancies. Graph A shows the combined pre-incubation U46619 data for normal pregnancy (N = 21) and PE (N = 14) from pitavastatin, pravastatin, and simvastatin experiments (at all concentrations), while Graph B shows post-incubation CPA data with control groups from PE and normal pregnancy. Replicate vessels from the same pregnancy were averaged for each group. Data are expressed as mean ± SEM, two-way ANOVA.

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  FIGURE 5. Effect of 2-h statin incubation on the contraction of CPAs from normal pregnancies. Assessment of U46619-induced contraction with either 1 µM pitavastatin (A, B) or 10 µM pitavastatin (C). There was no significant difference between the statin-exposed and control groups. Only when expressed as % KPSS was a significant decrease in contraction seen with 10 µM pitavastatin (D); p < 0.05. U46619 dose–response curves were compared using two-way ANOVA. Data are expressed as mean ± SEM; number of placentas in parentheses.

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  FIGURE 6. Effect of 2-h pitavastatin incubation on relaxation of CPAs from normal pregnancies. Assessment of CPA relaxation to SNP with either pitavastatin at 1 µM (A) or 10 µM pitavastatin (B). No significant effect was seen between the statin-exposed and control groups; p > 0.05. SNP dose–response curves were compared using two-way ANOVA with Sidak’s post hoc test, where applicable. Data are expressed as mean ± SEM; number of placentas in parentheses.

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  FIGURE 7. Effect of 2-h statin incubation on contraction of CPAs from PE pregnancies. Assessment of U46619-induced contraction with either 1 µM pitavastatin (A,B) or 10 µM pitavastatin (C). There was no significant effect when expressed as tension (kPa) or as % KPSS; p > 0.05. However, a significant effect was seen for 10 µM pitavastatin (D) when data were expressed as % KPSS; p < 0.05. U46619 dose–response curves were compared using two-way ANOVA with Sidak’s post hoc test, where applicable. Data are expressed as mean ± SEM; number of placentas in parentheses.***p < 0.001.

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  FIGURE 8. Effect of 2 hr statin incubation on relaxation of CPAs from PE pregnancies. Assessment of CPA relaxation to SNP with either 1 µM pitavastatin (A) or 10 µM pitavastatin (B), there was no significant effect on relaxation between statin-exposed and control groups; p > 0.05. SNP dose response curves were compared using two-way ANOVA. Data are expressed as mean ± SEM; number of placentas in parenthesis.