title: Transcriptional Profiling of Foam Cells Reveals Induction of Guanylate-Binding Proteins Following Western Diet Acceleration of Atherosclerosis in the Absence of Global Changes in Inflammation.
abstract: BACKGROUND
  Foam cells are central to two major pathogenic processes in atherogenesis: cholesterol buildup in arteries and inflammation. The main underlying cause of cholesterol deposition in arteries is hypercholesterolemia. This study aimed to assess, in vivo, whether elevated plasma cholesterol also alters the inflammatory balance of foam cells.
  
  
  RESULTS
  Apolipoprotein E-deficient mice were fed regular mouse chow through the study or were switched to a Western-type diet (WD) 2 or 14 weeks before death. Consecutive sections of the aortic sinus were used for lesion quantification or to isolate RNA from foam cells by laser-capture microdissection (LCM) for microarray and quantitative polymerase chain reaction analyses. WD feeding for 2 or 14 weeks significantly increased plasma cholesterol, but the size of atherosclerotic lesions increased only in the 14-week WD group. Expression of more genes was affected in foam cells of mice under prolonged hypercholesterolemia than in mice fed WD for 2 weeks. However, most transcripts coding for inflammatory mediators remained unchanged in both WD groups. Among the main players in inflammatory or immune responses, chemokine (C-X-C motif) ligand 13 was induced in foam cells of mice under WD for 2 weeks. The interferon-inducible GTPases, guanylate-binding proteins (GBP)3 and GBP6, were induced in the 14-week WD group, and other GBP family members were moderately increased.
  
  
  CONCLUSIONS
  Our results indicate that acceleration of atherosclerosis by hypercholesterolemia is not linked to global changes in the inflammatory balance of foam cells. However, induction of GBPs uncovers a novel family of immune modulators with a potential role in atherogenesis.
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, NY.
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Goo
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, NY.
authors.forename: Se-Hee
authors.initials: SH
authors.lastname: Son
authors.affiliation: Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Yechoor
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical College, Albany, NY paula@mail.amc.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Paul
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000139:chemically induced / Q000209:etiology*; D066273:Diet, Western / Q000009:adverse effects*; D005260:Female; D005487:Foam Cells / Q000737:chemistry* / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000032:analysis*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000503:physiopathology*; D061346:Laser Capture Microdissection; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012850:Sinus of Valsalva / Q000737:chemistry
chemical_list: D008055:Lipids; D019204:GTP-Binding Proteins
keywords: atherosclerosis; cholesterol; gene expression; inflammation; macrophages