435. Cardiovascular disease in the mother and offspring after preeclampsia in mice – Protective effects of pravastatin

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Preeclampsia (PE) has been associated with long-term increased risk for cardiovascular disease in women, suggesting that PE is more than an isolated disease of pregnancy. However, it is not known if this increased risk for these long-term diseases is due to factors developed during PE or to prepregnancy renal and cardiovascular risk factors commonly found in women that develop PE. We investigated if preeclampsia causes long-term cardiovascular consequences after pregnancy for mother and offspring. Using a mouse model in which wild type females with normal prepregnancy health develop PE, we investigated if factors that develop during the preeclamptic pregnancy affect future cardiovascular health of mother and offspring. In the mothers, endothelial dysfunction and hypertension were observed after PE. Furthermore, glomerular injury not only persisted but deteriorated after PE, leading to fibrosis. Left ventricular (LV) remodeling characterized by increased collagen I and MMP-9 deposition and enlarged cardiomyocytes were also detected after PE. Increased LV, internal wall thickness and mass, increased end-diastolic and end-systolic volumes, and increased stroke volume were observed after PE. Increased placenta-derived bioactive factors modulating vascular function, endothelin I and sFlt-1, markers of metabolic disease: leptin and insulin, vasoconstrictor isoprostane-8 and proinflammatory mediators IL-6 and complement C5a were increased in serum during and after a preeclamptic pregnancy. Interestingly, the offspring of PE-mice developed endothelial dysfunction, hypertension and signs of metabolic disease. Increased microglia activation, characterised by increased release of proinflammatory cytokines, was observed in the neonatal brains after PE suggesting neurogenic hypertension. Prevention of placental insufficiency with pravastatin, prevented the cardiovascular complications observed in the mother and offspring. In conclusion, placental-derived factors released during PE has long term health effects on the cardiovascular system of the mother and offspring independently of prepregnancy risk factors. Pravastatin therapy given during PE prevents long term health compromise.