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Publication

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 EA 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
Name Institution Edward Fisher New York University School of Medicine

Complications
All Complications Bioinformatics Bone Cardiomyopathy Cardiovascular Gastro-Intestinal (GI) Nephropathy Neuropathy & Neurocognition Pediatric Endocrinology Retinopathy Uropathy Wound Healing

Genes
Symbol Description Abca1 ATP-binding cassette, sub-family A (ABC1), member 1 Mcpt1 mast cell protease 1 Nr1h3 nuclear receptor subfamily 1, group H, member 3 Pparg peroxisome proliferator activated receptor gamma Ccl19 chemokine (C-C motif) ligand 19 Ccl2 chemokine (C-C motif) ligand 2 Ccr7 chemokine (C-C motif) receptor 7