Abstract

Introduction: Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by new-onset hypertension with new-onset proteinuria or other signs/symptoms of preeclampsia after 20 weeks’ gestation. It is associated with an increase in anti-angiogenic, oxidative, and pro-inflammatory factors including soluble fms-like tyrosine kinase-1 (sFLT-1). While a previous study established cumulative beneficial effects of resveratrol and pravastatin on cardiovascular disease, no study has been conducted regarding this combination therapy on PE. Hypothesis: The combination of resveratrol and pravastatin is more effective in reversing endothelial damage than the individual drugs alone. Methods: Human umbilical vein endothelial cells (HUVECs) were incubated with sFLT-1 (25ng/ml) for 24 hours. HUVECs were then treated with either 20μM resveratrol, 20μM pravastatin, 20μM resveratrol + 20μM pravastatin, or left untreated. Cells were lysed and western blotting was performed using primary antibodies against: eNOS, phospho-eNOS and NF-κB. Immunoreactive bands were visualized and quantified using Image Studio Lite Ver 5.2. Results: Pre-treatment with sFLT-1 increased expression of NF-κB compared to untreated controls (Mean±SEM: 53.57±24.98 vs 27.78±15.85 p=0.0346), while combination treatment of sFLT-1 pre-treated cells reduced expression of NF-κB (Mean: 53.57±24.98 vs 38.99±26.81 p=0.0186). eNOS expression was not changed by pre-treatment with sFLT-1, but expression was improved by pravastatin only in control cells (Mean: 3.084±0.6266 vs 4.737±1.247 p=0.0463). Phospho-eNOS expression was improved by pravastatin treatment in both control cells (Mean: 1.309±0.4633 vs 2.467±0.8298 p=0.0213) and in sFLT-1 pre-treated cells (Mean 1.235±0.3765 vs 2.716±0.9470 p=0.0347). Finally, phospho-eNOS expression was improved by combination treatment in control cells (Mean: 1.309±0.4633 vs 1.825±0.5793 p=0.0136). Conclusions: Our results show that treatment with resveratrol and pravastatin was more effective at decreasing inflammation than individual treatments, therefore suggesting that the combination therapy could be a helpful treatment for PE pathophysiology.

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