title: Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice.
abstract: BACKGROUND
  Sphingomyelin synthase 2 (SMS2) contributes to de novo sphingomyelin (SM) biosynthesis. Its activity is related to SM levels in the plasma and the cell membrane. In this study, we investigated the possibility of a direct relationship between SMS and atherosclerosis.
  
  
  METHODS
  The Adenovirus containing SMS2 gene was given into 10-week ApoE KO C57BL/6J mice by femoral intravenous injection. In the control group, the Adenovirus containing GFP was given. To confirm this model, we took both mRNA level examination (RT-PCR) and protein level examination (SMS activity assay).
  
  
  RESULTS
  We generated recombinant adenovirus vectors containing either human SMS2 cDNA (AdV-SMS2) or GFP cDNA (AdV-GFP). On day six after intravenous infusion of 2 × 10(11) particle numbers into ten-week-old apoE KO mice, AdV-SMS2 treatment significantly increased liver SMS2 mRNA levels and SMS activity (by 2.7-fold, 2.3-fold, p < 0.001, respectively), compared to AdV-GFP treated mice. Moreover, plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and sphingomyelin (SM) levels were significantly increased by 39% (p < 0.05), 42% (p < 0.05), 68% (p < 0.001), and 45% (p < 0.05), respectively. Plasma high-density lipoprotein cholesterol (HDL-C), phosphatidylcholine (PC), and PC/SM ratio were decreased by 42% (p < 0.05), 18% (p < 0.05), and 45% (p < 0.05), respectively. On day 30, the atherosclerotic lesions on the aortic arch of AdV-SMS2 treated mice were increased, and the lesion areas on the whole aorta and in the aortic root were significantly increased (p < 0.001). Furthermore, the collagen content in the aorta root was significantly decreased (p < 0.01).
  
  
  CONCLUSIONS
  Our results present direct morphological evidence for the pro-atherogenic capabilities of SMS2. SMS2 could be a potential target for treating atherosclerosis.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
authors.forename: Jibin
authors.initials: J
authors.lastname: Dong
authors.forename: Yarui
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Manping
authors.initials: M
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D004041:Dietary Fats / Q000008:administration & dosage; D057075:Enzyme Assays; D005822:Genetic Vectors; D006801:Humans; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D008055:Lipids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C455440:SGMS1 protein, human; D017855:Transferases (Other Substituted Phosphate Groups)