title: Characterization of monocyte chemoattractant proteins and CC chemokine receptor 2 expression during atherogenesis in apolipoprotein E-null mice.
abstract: OBJECTIVE
  We aimed to investigate the expression of monocyte chemoattractant proteins (MCPs) and their cognate receptor CC chemokine receptor 2 (CCR2) in aortas of apolipoprotein E-null (apoE(-/-)) mice during atherogenesis as well as the possible transcription pathway involved in the early induction of MCP-1 in vascular smooth muscle cells (VSMCs) in vivo.
  
  
  METHODS
  Atherosclerotic lesion development, aortic MCPs and CCR2 mRNA expression as well as the cellular localization of MCP-1, CCR2 and MCP-1 related transcription factors in atherosclerotic lesions were analyzed in apoE(-/-) mice fed a high fat and cholesterol diet.
  
  
  RESULTS
  MCP-1 and CCR2 mRNA expression was significantly induced during early atherogenesis and peaked after 10 and 12 weeks of diet, respectively, whereas MCP-2 and MCP-3 mRNA expression elevated in the late phases of lesion development. Immunostaining revealed that early MCP-1 expression was localized to VSMCs and that, in advanced lesions, both neointimal VSMCs and intimal macrophages expressed high levels of MCP-1. During the early (0 and 4 weeks of diet) induction of MCP-1 in VSMCs, the regulatory activator protein-1 (AP-1) proteins c-Jun and c-Fos were highly expressed and observed within the VSMCs nuclei, whereas nuclear factor-κB (NF-κB) protein p65 was only observed within the nuclei of VSMCs after 4 weeks of diet. CCR2 was also identified on intimal macrophages, endothelial cells and VSMCs in advanced lesions.
  
  
  CONCLUSIONS
  This study provides fundamental information on the expression kinetics of MCPs and CCR2 during atherogenesis and indicates that the earliest induction of MCP-1 in VSMCs of apoE(-/-)mice appears to correlate with AP-1 but not NF-κB regulatory pathways.
authors.affiliation: The Key Laboratory of Animal Resistant Biology of Shandong, College of Life Sciences, Shandong Normal University, Jinan, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Guocheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D050197:Atherosclerosis / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D054390:Receptors, CCR2 / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D017931:DNA Primers; D018945:Monocyte Chemoattractant Proteins; D054390:Receptors, CCR2