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Growth differentiation factor-15 regulates oxLDL-induced lipid homeostasis and autophagy in human macrophages

Kathrin Ackermann1, Gabriel A Bonaterra1, Ralf Kinscherf1

  • 1Institute for Anatomy and Cell Biology, Department of Medical Cell Biology, Philipps-University of Marburg, 35032, Marburg, Germany.

Atherosclerosis
|January 19, 2019
PubMed
Abstract

Insights

Growth Differentiation Factor-15 (GDF-15) combined with oxidized-low density lipoprotein (oxLDL) impairs autophagy and lipid homeostasis in human macrophages (MΦ). This suggests GDF-15 plays a role in atherosclerotic plaque development.

Area of Science:

  • Cardiovascular Biology
  • Cellular Metabolism
  • Molecular Medicine

Background:

  • Growth Differentiation Factor-15 (GDF-15) is linked to cardiovascular disease, inflammation, and atherosclerosis.
  • GDF-15 is highly expressed in macrophages within atherosclerotic lesions.

Purpose of the Study:

  • To investigate the influence of GDF-15 on lipid homeostasis and autophagy in human macrophages during foam cell formation.
  • To elucidate the role of GDF-15 in the context of oxidized-low density lipoprotein (oxLDL) exposure.

Main Methods:

  • Human THP-1 macrophages were treated with oxidized-low density lipoprotein (oxLDL) and/or recombinant GDF-15 (rGDF-15).
  • GDF-15 was transiently silenced (siGDF-15) or control siRNA (nsiGDF-15) was used.
  • Lipid accumulation was assessed using Oil Red O staining.
  • Autophagy-related proteins (Atg5, Atg12/Atg5, p62) were analyzed via Western blot and confocal microscopy.

Main Results:

  • rGDF-15, alone and with oxLDL, significantly increased lipid accumulation in macrophages.
  • Silencing GDF-15 reduced lipid accumulation.
  • Co-incubation with rGDF-15 and oxLDL increased autophagy-related proteins (Atg5, Atg12/Atg5) and p62 accumulation.
  • siGDF-15 MΦ showed reduced p62 accumulation compared to controls.

Conclusions:

  • GDF-15, particularly with oxLDL, impairs autophagic processes in human macrophages.
  • This impairment has consequences for lipid homeostasis.
  • GDF-15 has a novel pathophysiological role in atherosclerotic plaque development and progression.
Keywords:
ATG5AutophagyGDF-15oxLDLp62

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