| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States; Statistics, Korea University, Seoul, Korea, Republic of
2 Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States
3 Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States; Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States
4 Public Health Sciences, University of Virginia, Charlottesville, Virginia, United States
5 Medicine, UCSD, San Diego, California, United States
6 Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States; Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, United States; Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States
* To whom correspondence should be addressed. E-mail: klausley{at}virginia.edu.
Foam cell formation from monocyte-derived macrophages is a hallmark of atheroscle-rotic lesions. Aspects of this process can be recapitulated in vitro by exposing MCSF-induced or platelet factor 4 (CXCL4)-induced macrophages to oxidized (ox) or minimally modified (mm) low density lipoprotein (LDL). We measured gene expression in peripheral blood mononuclear cells (PBMCs), monocytes and macrophages treated with CXCL1 (GRO-
) or CCL2 (MCP-1) as well as foam cells induced by native LDL, mmLDL or oxLDL using 22 Affymetrix gene chips. Using an advanced Bayesian error-pooling approach and a heterogeneous error model (HEM) with a false discovery rate (FDR) <0.05, we found 5,303 of 22,215 probe sets to be significantly regulated in at least one of the conditions. Among a subset of 917 candidate genes that were preselected for their known biological functions in macrophage foam-cell differentiation, we found that 290 genes met the above statistical criteria for significant differential expression patterns. While many expected genes were found to be upregulated by LDL and oxLDL, very few were induced by mmLDL. We also found induction of unexpected genes, most strikingly MHC-II and other dendritic cell markers such as CD11c. The gene expression patterns in response to oxLDL were similar in MCSF-induced and CXCL4-induced macrophages. Our findings suggest that LDL and oxLDL, but not mmLDL, induce a dendritic cell-like phenotype in macrophages, suggesting that these cells may be able to present antigens and support an immune response.
This article has been cited by other articles:
|
|
 |
|
  C. A. Gleissner, J. M. Sanders, J. Nadler, and K. Ley Upregulation of Aldose Reductase During Foam Cell Formation as Possible Link Among Diabetes, Hyperlipidemia, and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1137 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Strissel, Z. Stancheva, H. Miyoshi, J. W. Perfield II, J. DeFuria, Z. Jick, A. S. Greenberg, and M. S. Obin Adipocyte Death, Adipose Tissue Remodeling, and Obesity Complications Diabetes, December 1, 2007; 56(12): 2910 - 2918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Gleissner, N. Leitinger, and K. Ley Effects of Native and Modified Low-Density Lipoproteins on Monocyte Recruitment in Atherosclerosis Hypertension, August 1, 2007; 50(2): 276 - 283. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
