Adenovirus-mediated overexpression of sphingomyelin synthases 1 and 2 increases the atherogenic potential in mice.

Journal of Lipid Research
Jibin DongXian-Cheng Jiang

Abstract

Sphingomyelin synthase 1 (SMS1) and SMS2 are two isoforms of SMS, the last enzyme for sphingomyelin (SM) biosynthesis. To evaluate the role of SMS in vivo in terms of plasma lipoprotein metabolism, we generated recombinant adenovirus vectors containing human SMS1 cDNA (AdV-SMS1), SMS2 cDNA (AdV-SMS2), or the reporter LacZ cDNA (AdV-LacZ) as a control. On day 7 after intravenous infusion of 2 x 10(11) particles of both AdV-SMS1 and AdV-SMS2 into mice, liver SMS1 and SMS2 mRNA levels as well as SMS activity were significantly increased (2.5-, 2.7-, 2.1-, and 2.3-fold, respectively; P < 0.001). Lipoprotein analysis indicated that AdV-SMS1 and AdV-SMS2 treatment caused no changes of total SM and cholesterol levels but significantly decreased HDL-SM and HDL-cholesterol (42% and 38%, and 27% and 25%, respectively; P < 0.05). It also significantly increased non-HDL-SM and non-HDL-cholesterol levels (50% and 35%, and 64% and 61%, respectively; P < 0.05) compared with AdV-LacZ controls. SDS-PAGE showed a significant increase in apolipoprotein B (apoB; P < 0.01) but no changes in apoA-I levels. Moreover, we found that non-HDL from both AdV-SMS1- and AdV-SMS2-treated mice was significantly aggregated after treatment with a mammalian sphin...Continue Reading

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