PMID- 18628255
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20220310
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 80
IP  - 2
DP  - 2008 Nov 1
TI  - P55 tumour necrosis factor receptor in bone marrow-derived cells promotes 
      atherosclerosis development in low-density lipoprotein receptor knock-out mice.
PG  - 309-18
LID - 10.1093/cvr/cvn193 [doi]
AB  - AIMS: Tumour necrosis factor (TNF) is a pivotal pro-inflammatory cytokine with a 
      clear pathogenic role in many chronic inflammatory diseases, and p55 TNF receptor 
      (TNFR) mediates the majority of TNF responses. The aim of the current study was 
      to investigate the role of p55 TNFR expression in bone marrow-derived cells, in 
      atherosclerotic lesion development. METHODS AND RESULTS: Irradiated low-density 
      lipoprotein receptor knock-out mice were reconstituted with either p55 TNFR 
      knock-out or control haematopoietic stem cells to generate chimeras deficient or 
      wild-type for p55 TNFR specifically in bone marrow-derived cells, including 
      macrophages. Upon high fat feeding, p55 TNFR knock-out transplanted mice 
      developed smaller atherosclerotic lesions. These lesions were characterized by 
      the presence of smaller foam cells and a reduced macrophage foam cell area. They 
      did not differ in other compositional characteristics as determined by 
      quantification of inflammatory T-cell and neutrophil influx, apoptotic and 
      necrotic cell death, and collagen content. In vitro studies confirmed a 
      significant defect in modified lipoprotein endocytosis by p55 TNFR knock-out 
      macrophages due to reduced scavenger receptor class A expression. Interestingly, 
      plasma cytokine/chemokine profile analysis indicated that monocyte 
      chemoattractant protein-1 (MCP-1) levels, a major chemokine involved in 
      atherogenesis, were consistently and significantly lower in p55 TNFR knock-out 
      transplanted mice compared with controls, before and after high fat feeding. 
      CONCLUSION: p55 TNFR expression in bone marrow-derived cells contributes to the 
      development of atherosclerosis by enhancing lesional foam cell formation and by 
      promoting the expression of pro-atherosclerotic chemokines such as MCP-1.
FAU - Xanthoulea, Sofia
AU  - Xanthoulea S
AD  - Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, 
      Maastricht University, Universiteitssingel 50, UNS 50/11, 6229ER Maastricht, The 
      Netherlands. s.xanthoulea@gen.unimaas.nl
FAU - Gijbels, Marion J J
AU  - Gijbels MJ
FAU - van der Made, Ingeborg
AU  - van der Made I
FAU - Mujcic, Hilda
AU  - Mujcic H
FAU - Thelen, Melanie
AU  - Thelen M
FAU - Vergouwe, Monique N
AU  - Vergouwe MN
FAU - Ambagts, Matheus H C
AU  - Ambagts MH
FAU - Hofker, Marten H
AU  - Hofker MH
FAU - de Winther, Menno P J
AU  - de Winther MP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080715
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, LDL)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Scavenger Receptors, Class A)
RN  - 0 (Tnfrsf1a protein, mouse)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/immunology/*metabolism/pathology
MH  - Bone Marrow Cells/immunology/*metabolism
MH  - *Bone Marrow Transplantation
MH  - Chemokine CCL2/blood
MH  - Disease Models, Animal
MH  - Endocytosis
MH  - Foam Cells/immunology/*metabolism/pathology
MH  - Inflammation Mediators/blood
MH  - Interleukin-6/metabolism
MH  - Lipid Metabolism
MH  - Liver/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, LDL/*deficiency/genetics
MH  - Receptors, Tumor Necrosis Factor, Type I/deficiency/genetics/*metabolism
MH  - Scavenger Receptors, Class A/metabolism
MH  - Time Factors
EDAT- 2008/07/17 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/07/17 09:00
PHST- 2008/07/17 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/07/17 09:00 [entrez]
AID - cvn193 [pii]
AID - 10.1093/cvr/cvn193 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2008 Nov 1;80(2):309-18. doi: 10.1093/cvr/cvn193. Epub 2008 Jul 
      15.