Simvastatin Alleviates Pathology in a Rat Model of Preeclampsia Involving ERK/MAPK Pathway

Preeclampsia (PE) is a pregnancy-specific condition characterized by new-onset hypertension. There is evidence suggesting that imbalances of angiogenic factors, oxidative stress, and inflammation may be central to the pathogenesis of PE. We sought to investigate whether simvastatin would reduce mean arterial pressure, restore the angiogenic balance, and ameliorate inflammation and oxidative stress in a nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME)-induced rat model of PE. We found that blood pressure was significantly increased in the l-NAME group compared to normal pregnant dams (P < .01), and simvastatin reduced this difference. In addition, dams from the l-NAME group showed lower vascular endothelial growth factor (VEGF) and interleukin (IL) 10 levels and higher plasma-soluble FMS-like tyrosine kinase 1 (sFlt-1), tumor necrosis factor (TNF-), and oxidative stress marker malondialdehyde (MDA) levels as compared to control dams (P < .01, for all). Interestingly, simvastatin treatment significantly increased VEGF and IL-10 levels while decreased sFlt-1, TNF-, and MDA levels compared to the untreated l-NAME group. Moreover, simvastatin treatment significantly upregulated protein expression of placental p-extracellular signal-regulated kinase (ERK1), p-p38 mitogen-activated protein kinase (MAPK), p-c-Jun N-terminal kinase, and p-protein kinase B compared to untreated l-NAME control. These results suggest that simvastatin treatment restores angiogenic balance and ameliorates inflammation and oxidative stress in a rat model of PE involving ERK/MAPK pathway.