Gene expression changes in foam cells and the role of chemokine receptor CCR7
during atherosclerosis regression in ApoE-deficient mice.
Authors Trogan E, Feig JE, Dogan S, Rothblat GH, Angeli V, Tacke F, Randolph GJ, Fisher
Submitted By Edward Fisher on 2/23/2009
Status Published
Journal Proceedings of the National Academy of Sciences of the United States of America
Year 2006
Date Published 3/7/2006
Volume : Pages 103(10) : 3781 - 3786
PubMed Reference 16537455
Abstract Atherosclerosis regression is an important clinical goal. In previous studies of
regression in mice, the rapid loss of plaque foam cells was explained by
emigration to lymph nodes, a process reminiscent of dendritic cells. In the
present study, plaque-containing arterial segments from apoE-/- mice were
transplanted into WT recipient normolipidemic mice or apoE-/- mice. Three days
after transplant, in the WT regression environment, plaque size decreased by
approximately 40%, and foam cell content by approximately 75%. In contrast, both
parameters increased in apoE-/- recipients. Foam cells were isolated by laser
capture microdissection. In WT recipients, there were 3- to 6-fold increases in
foam cells of mRNA for liver X receptor alpha and cholesterol efflux factors
ABCA1 and SR-BI. Although liver X receptor alpha was induced, there was no
detectable expression of its putative activator, peroxisome
proliferator-activated receptor gamma. Expression levels of VCAM or MCP-1 were
reduced to 25% of levels in pretransplant or apoE-/- recipient samples, but
there was induction at the mRNA and protein levels of chemokine receptor CCR7,
an essential factor for dendritic cell migration. Remarkably, when CCR7 function
was abrogated in vivo by treatment of WT recipients with antibodies to CCR7
ligands CCL19 and CCL21, lesion size and foam cell content were substantially
preserved. In summary, in foam cells during atherosclerosis regression, there is
induction of CCR7 and a requirement for its function. Taken with the other gene
expression data, these results in vivo point to complex relationships among the
immune system, nuclear hormone receptors, and inflammation during regression.

Investigators with authorship
Edward FisherNew York University School of Medicine


Abca1ATP-binding cassette, sub-family A (ABC1), member 1
Mcpt1mast cell protease 1
Nr1h3nuclear receptor subfamily 1, group H, member 3
Ppargperoxisome proliferator activated receptor gamma
Ccl19chemokine (C-C motif) ligand 19
Ccl2chemokine (C-C motif) ligand 2
Ccr7chemokine (C-C motif) receptor 7