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Adenovirus-mediated sphingomyelin synthase 2 increases atherosclerotic lesions in ApoE KO mice

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). RESULT: 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 x 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 Keywords : Adenoviridae,administration & dosage,Animals,Aorta,Apolipoproteins E,Atherosclerosis,biosynthesis,blood,China,Dietary Fats,Enzyme Assays,Genetic Vectors,genetics,Humans,Lipids,Liver,Membrane Proteins,metabolism,methods,Mice,Mice,Inbred C57BL,Mice,Knockout,Nerve Tissue Proteins,pathology,Recombinant Proteins,Transferases (Other Substituted Phosphate Groups),, Sphingomyelin,Synthase2,Increases,Atherosclerotic, sciatica specialist london

Date of Publication : 2011 Jan 17

Authors : Wang X;Dong J;Zhao Y;Li Y;Wu M;

Organisation : School of Pharmacy, Fudan University, Shanghai, China

Journal of Publication : Lipids Health Dis

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21235823

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