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Cardiovasc Res. 2014 Dec 1;104(3):467-76. doi: 10.1093/cvr/cvu213. Epub 2014 Sep 24.

PKCδ is dispensible for oxLDL uptake and foam cell formation by human and murine macrophages.

Author information

1
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, Amsterdam 1066CX, The Netherlands k.szilagyi@sanquin.nl.
2
Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
3
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, Amsterdam 1066CX, The Netherlands.
4
The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
5
INSERM U1035, Université Bordeaux Segalen, Bordeaux, France.
6
Divison of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
7
Divison of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
8
Hôpital Femme Mère Enfant, Hospices Civils de Lyon and Université de Lyon, Lyon, France.
9
Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, Amsterdam 1066CX, The Netherlands Department of Pediatric Hematology, Immunology and Infectious Disease, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
10
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
11
Department of Medical Biochemistry, Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Abstract

AIMS:

Uptake of oxidized lipoprotein particles (oxLDL) and foam cell formation by macrophages is one of the first steps in the development of atherosclerosis. Recently, protein kinase C δ (PKCδ) has been implicated as a regulator of oxLDL uptake and foam cell formation via down-regulation of PKCβ and scavenger receptors CD36 and SR-A expression. Here, we describe studies in which we have re-evaluated the role of PKCδ in oxLDL uptake and foam cell formation.

METHODS AND RESULTS:

PKCδ expression was silenced in the human monocytic cell lines and also in primary human monocytes to analyse oxLDL uptake and CD36 expression. Additionally, bone marrow-derived macrophages of PKCδ knockout mice and macrophages cultured from patients with rare null mutations in the PRKCD gene were tested for uptake of oxLDL and foam cell formation. Expression of scavenger receptor CD36 was determined and levels of PKCβ isoforms were quantified. Neither a reduction in PKCδ levels nor its complete absence resulted in a detectable effect on the uptake of oxLDL and the formation of foam cells.

CONCLUSION:

PKCδ is dispensible for oxLDL uptake and foam cell formation by monocytes and macrophages.

KEYWORDS:

Foam cell; OxLDL uptake; PKCδ deficiency; Protein kinase Cδ

PMID:
25253077
DOI:
10.1093/cvr/cvu213
[Indexed for MEDLINE]

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