Postprandial apoE Isoform and Conformational Changes Associated with VLDL Lipolysis Products Modulate Monocyte Inflammation

Laura J. den Hartigh, Robin Altman, Romobia Hutchinson, Jitka Petrlova, Madhu S. Budamagunta, Sarada D. Tetali, Jens O. Lagerstedt, John C Voss, John C Rutledge

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: Postprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation. Methods and Results: We showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4. Conclusion: Postprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation.

Original languageEnglish (US)
Article numbere50513
JournalPLoS One
Volume7
Issue number11
DOIs
StatePublished - Nov 28 2012

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VLDL Lipoproteins
very low density lipoprotein
Lipolysis
lipolysis
Apolipoproteins E
Apolipoprotein E3
monocytes
lipopolysaccharides
Lipopolysaccharides
Monocytes
Protein Isoforms
inflammation
Apolipoprotein E4
Inflammation
fasting
Fasting
blood vessels
Bearings (structural)
Spin Labels
Ego

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Postprandial apoE Isoform and Conformational Changes Associated with VLDL Lipolysis Products Modulate Monocyte Inflammation. / den Hartigh, Laura J.; Altman, Robin; Hutchinson, Romobia; Petrlova, Jitka; Budamagunta, Madhu S.; Tetali, Sarada D.; Lagerstedt, Jens O.; Voss, John C; Rutledge, John C.

In: PLoS One, Vol. 7, No. 11, e50513, 28.11.2012.

Research output: Contribution to journalArticle

den Hartigh, LJ, Altman, R, Hutchinson, R, Petrlova, J, Budamagunta, MS, Tetali, SD, Lagerstedt, JO, Voss, JC & Rutledge, JC 2012, 'Postprandial apoE Isoform and Conformational Changes Associated with VLDL Lipolysis Products Modulate Monocyte Inflammation', PLoS One, vol. 7, no. 11, e50513. https://doi.org/10.1371/journal.pone.0050513
den Hartigh, Laura J. ; Altman, Robin ; Hutchinson, Romobia ; Petrlova, Jitka ; Budamagunta, Madhu S. ; Tetali, Sarada D. ; Lagerstedt, Jens O. ; Voss, John C ; Rutledge, John C. / Postprandial apoE Isoform and Conformational Changes Associated with VLDL Lipolysis Products Modulate Monocyte Inflammation. In: PLoS One. 2012 ; Vol. 7, No. 11.
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