Statines Reduce Cardiac Dysfunction After Preeclamptic Pregnancy

Introduction: Former preeclamptic women have an increased risk of cardiovascular disease in later life. However, the underlying functional and structural mechanisms are still unknown. Objective: We tested the hypothesis that pravastatin has a beneficial effect on the remodeling of the maternal heart after preeclamptic pregnancy and thus reduces the long-term cardiovascular risk. Methods: Female rats harboring the human angiotensinogen gene [TGR(hAogen)L1623] developed a preeclamptic phenotype during pregnancy when mated with male rats carrying the human renin gene [TGR(hRen)L10J], but behaved physiologically normal postpartum. To investigate a possible intervention, we treated preeclamptic dams with pravastatin for four weeks after birth, which was started already during pregnancy. Cardiac structure and function was compared by speckle tracking echocardiography, gene expression analysis, and immune staining of the maternal heart. Results: Due to pravastatin treatment, former preeclamptic rats reduced signs of cardiac hypertrophy (perimeter cardiomyocytes 65.3±0.3 vs. 60.5±0.5 μm), fibrosis (fibronectin 3.9±0.3 vs. 1.8±0.2 %) and improved cardiac microcirculation (CD31+ cells 219.0±4.7 vs. 269.1±8.6). In addition, cardiac output was increased postpartum by statin treatment (ejection fraction 57.2±1.2 vs. 61.0±1.9; global longitudinal strain -14.5±0.6 vs. -19.8±1.0 %; heartrate 355.0±8.7 vs. 328.6±8.3 bpm). Analysis of maternal blood serum showed a reduction of brain natriuretic peptide (BNP 0.39±0.05 vs. 0.33±0.01 ng/ml) and soluble fms-like tyrosine kinase 1 (sFlt1 0.69±0.02 vs. 0.51±0.02 ng/ml) even four weeks after birth. Fetuses at the time of birth also benefited from treatment (brain liver ratio 0.93±0.03 vs. 0.82±0.01; heart body ratio 7.14±0.09 vs. 6.80±0.12). Discussion: Former preeclamptic rats showed significant cardiac hypertrophy in combination with fibrosis and capillary rarefaction. These irreversible structural changes can be reduced by pravastatin treatment. We could not detect any harmful influence of statins on the fetus. Values mean±SEM, PE vs. PE+pravastatin