title: Sphingomyelin synthase 2 over-expression induces expression of aortic inflammatory biomarkers and decreases circulating EPCs in ApoE KO mice.
abstract: OBJECTIVE
  This study sought to assess the effect of sphingomyelin synthase 2 (SMS2) over-expression on plaque component and endothelial dysfunction in atherosclerosis.
  
  
  METHODS
  We generated recombinant adenovirus vectors containing human SMS2 cDNA (AdV-SMS2) or control gene GFP cDNA (AdV-GFP). Both AdVs were injected (i.v.) into ApoE KO mice to establish SMS2 over-expressing and control mice models, respectively. The mice were fed a high fat diet for 30 days. We then examined their plasma lipid levels, expression levels of aortic inflammatory biomarkers critical for the plaque's stability, and numbers of peripheral endothelial progenitor cells (EPC).
  
  
  RESULTS
  Compared with the control mice, SMS2 over-expression had significantly (1) increased aortic matrix metalloproteinase-2 (MMP-2), monocyte chemoattractant protein-1 (MCP-1), tissue factor (TF) and cyclooxygenase-2 (COX-2) mRNA levels (1.9-fold, 2.2-fold, 2.6-fold and 3.2-fold, respectively, P<0.01) and protein levels (2.2-fold, 1.9-fold, 1.9-fold and 2.1-fold, respectively, P<0.01); (2) increased MMP-2, COX-2 in situ expression in aortic root (2.6-fold and 2.3-fold, respectively, P<0.01); (3) decreased aortic COX-1 mRNA levels (65%, P<0.01) and protein levels (64%, P<0.01); and (4) decreased CD34/KDR-positive cells (33%, P<0.01), circulating angiogenic cells (CACs) (50%, P<0.05), and colony forming units (CFUs) (40%, P<0.05) in circulation.
  
  
  CONCLUSIONS
  SMS2 over-expression was probably associated with increased expression of aortic inflammatory biomarkers, as well as decreased numbers of CD34/KDR-positive cells, CACs and CFUs in circulation. Therefore, SMS2 over-expression might correlate with endothelial dysfunction and aggravate atherosclerotic plaque instability in ApoE KO mice.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Ya-Rui
authors.initials: YR
authors.lastname: Zhao
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Dong
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Man-Ping
authors.initials: MP
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C455440:SGMS1 protein, human; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse