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May 17, 2019

87th EAS Congress

02 - SUPRAPHYSIOLOGICAL MATERNAL HYPERCHOLESTEROLEMIA ASSOCIATES WITH INCREASED MATERNAL LEVELS OF PCSK9 AND WITH CHANGES IN THE MATERNAL AND NEONATAL LDL AND HDL PROFILE

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maternal hypercholesterolemia

PCSK9

HDL function

Abstract

Abstract

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Keywords

maternal hypercholesterolemia

PCSK9

HDL function

Abstract

Introduction: Physiological maternal hypercholesterolemia (MPH; total cholesterol (TC)≤280 mg/dL) occurs during pregnancy. However, some women develop supraphysiological maternal hypercholesterolemia (MSPH; TC>280 mg/dL) which associates with increased levels of LDL and leads to fetal endothelial dysfunction and atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL levels. It is unknown whether (1) PCSK9 is modulated in MSPH and (2) if MSPH associates with changes in maternal and neonatal lipoproteins functions, favoring a pro-atherogenic profile. Aims: To determine the levels of PCSK9 as well as the protein composition and function of maternal and neonatal lipoproteins in MSPH. Methods: PCSK9 was determined in maternal and umbilical cord serum from MPH (n=43) and MSPH (n=37) by ELISA. Lipoproteins were purified by ultracentrifugation. Protein were evaluated by western blot. The pro/anti-oxidant capacity was determined by reactive oxygen species (ROS) formation. Cholesterol efflux was evaluated in cells incubated with maternal and neonatal HDL. The activity of nitric oxide synthase (NOS) was evaluated by HPLC. Results: PCSK9 increased (12.7±0.5%) in maternal MSPH serum and correlated positively with TC (R2=0,118) and LDL (R2=0,198). LDL from MSPH women showed increased pro-oxidant activity (43.8±7.8%). HDL showed lower ApoE (33.4±3.6%) and PON1 (44.4±7.8%) protein abundance and increased antioxidant capacity (28.7±3.5%). Neonatal HDL from MSPH showed increased PON1 abundance (57.9±8.9%), but reduced antioxidant capacity (28.1±2.7%), reduced NOS activity induction (80.4±30%) and increased cholesterol efflux capacity (23.4±5.7%). Conclusion: MSPH associates with increased maternal levels of PCSK9 and changes in the maternal and neonatal lipoprotein function which could be involved in its pathogenesis.

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© Copyright 2019 Morressier GmbH.
All rights reserved.