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Modified lipoprotein-induced sFlt1 production in human placental trophoblasts is mediated by protein kinase C

  • 0Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, UK.
European Journal of Pharmacology +

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November 17, 2024

|

November 17, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Modified lipoproteins increase soluble fms-like tyrosine kinase-1 (sFlt1) in placental cells through protein kinase C (PKC) signaling. This pathway, involving PKC alpha and beta, may offer therapeutic targets for preeclampsia in diabetic women.

Area Of Science

  • Reproductive biology
  • Endocrinology
  • Molecular medicine

Background

  • Preeclampsia is common in diabetic pregnancies, with unclear mechanisms.
  • Oxidized, glycated lipoproteins previously shown to upregulate soluble fms-like tyrosine kinase-1 (sFlt1).
  • sFlt1 is a key mediator implicated in preeclampsia pathogenesis.

Purpose Of The Study

  • To investigate the role of protein kinase C (PKC) and its subtypes in regulating sFlt1 in placental trophoblasts.
  • To determine if PKC mediates the effect of modified lipoproteins on sFlt1.

Main Methods

  • Human trophoblast cell lines (HTR8/SVneo, BeWo) were treated with a PKC activator (PMA) and various PKC inhibitors.
  • The impact of heavily oxidized, glycated low-density lipoproteins (HOG-LDL) versus native LDL (N-LDL) and high glucose was assessed.
  • sFlt1 secretion, mRNA expression, and cellular PKC activity were measured.

Main Results

  • PMA significantly increased sFlt1 release and mRNA, inhibited by PKC inhibitors (GF109203X, Ro31-8220, LY333531).
  • HOG-LDL, not high glucose, enhanced PKC activity and increased sFlt1 secretion and mRNA.
  • The HOG-LDL-induced sFlt1 upregulation was blocked by the same PKC inhibitors.

Conclusions

  • Modified lipoproteins upregulate sFlt1 in trophoblasts via a PKC-dependent pathway, involving PKC alpha and beta isoforms.
  • This mechanism highlights potential therapeutic targets for reducing preeclampsia risk in diabetic women.

Keywords:

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