The role of proprotein convertase subtillisin/kexin type 9 in placental salvage and lipid metabolism in women with preeclampsia

Arthur Jason Vaught, Theresa Boyer, Efthymios Ziogos, Nuria Amat-Codina, Anum Minhas, Kristin Darwin, Alexia Debrosse, Neal Fedarko, Irina Burd, Ahmet Baschat, Garima Sharma, Allison G. Hays, Sammy Zakaria, Thorsten M. Leucker

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Preeclampsia is associated with decreased maternal low-density lipoprotein cholesterol (LDL-c), which is essential for fetal growth. The underlying mechanisms for decreased LDL-c in preeclampsia remain unknown. Proprotein convertase subtillisin/kexin type 9 (PCSK9) regulates serum LDL-c via LDL receptor (LDL-R) degradation. We describe the possible role of PCSK9 in lipid metabolism in all compartments of the parturient (maternal blood, placental tissue, and fetal blood) in pregnancies with and without preeclampsia. Methods: This is an observational study examining PCSK9 levels in maternal sera, umbilical cord blood, and PCSK9 protein content in placental tissue in three different locations (maternal placental interface, fetal placental interface, and umbilical cord) in women with and without preeclampsia at >23 weeks gestation. Results: 68 parturients with preeclampsia and 55 without preeclampsia were enrolled. Maternal serum LDL-c (116.6 ± 48.9 mg/dL vs 146.1 ± 47.1 mg/dL, p = 0.0045) and PCSK9 (83 [61.8127.6] ng/mL vs 105.3 [83.5142.9] ng/mL, p = 0.011) were also reduced in the preeclamptics versus controls. There were no differences in PCSK9 protein content between preeclamptics and controls at comparative placental interfaces. However, PCSK9 protein content increased between the preeclampsia maternal placental interface (1.87 ± 0.62) and the preeclampsia umbilical cord (2.67 ± 1.08, p = 0.0243). Discussion: PCSK9 levels are lower in maternal sera in preeclampsia when compared to controls. Placental PCSK9 protein content in preeclampsia increases from the maternal interface to the umbilical cord; however, this is not seen in controls. This suggests a potential compensatory mechanism for PCSK9 which allows for higher circulating fetal LDL-c levels in preeclampsia.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalPlacenta
Volume132
DOIs
StatePublished - Feb 2023

Keywords

  • Lipid metabolism
  • Preeclampsia
  • Proprotein convertase subtillisin/kexin type 9

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology

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