Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia

Hiten D Mistry1,2, Lesia O Kurlak2, Yosef T Mansour3

  • 1Department of Nephrology, Hypertension, Clinical Pharmacology, and Clinical Research, University of Bern, Bern, Switzerland hiten.mistry@nottingham.ac.uk.

Insights

Preeclampsia alters cholesterol processing in maternal and fetal plasma, with decreased ABCA1 efflux but increased HDL efflux. Placental CYP27A1 and 27-OHC also increase, potentially as a protective response.

Area of Science:

  • Cardiovascular Biology
  • Reproductive Medicine
  • Metabolic Disorders

Background:

  • Preeclampsia is a pregnancy complication linked to future cardiovascular disease.
  • Reduced cholesterol efflux capacity is associated with cardiovascular disease.
  • Investigating cholesterol transport in preeclampsia may reveal mechanisms for cardiovascular risk.

Purpose of the Study:

  • To investigate maternal and fetal plasma cholesterol efflux capacity in preeclampsia.
  • To examine placental expression of sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP).
  • To explore the role of cholesterol metabolism in preeclampsia pathophysiology and cardiovascular risk.

Main Methods:

  • Measured total, HDL-, and ABCA1-mediated cholesterol effluxes using maternal and fetal plasma.
  • Quantified apolipoproteins (apoA1, apoE) and 27-hydroxycholesterol (27-OHC).
  • Assessed placental expression and localization of key proteins (CYP27A1, AIBP, apoA1, apoE, SRB1) via immunohistochemistry.

Main Results:

  • Preeclampsia showed increased maternal/fetal total and HDL-mediated cholesterol efflux, but decreased ABCA1-mediated efflux.
  • Elevated maternal/fetal apoE and placental CYP27A1, AIBP, and 27-OHC concentrations were observed in preeclampsia.
  • Fetal plasma 27-OHC levels were decreased in preeclamptic samples.

Conclusions:

  • Preeclampsia disrupts cholesterol efflux pathways, with altered ABCA1 and HDL mediation.
  • Increased placental CYP27A1 and 27-OHC may represent a compensatory mechanism to manage cholesterol.
  • These findings suggest potential pathways linking preeclampsia to later cardiovascular risk.

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