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Sphingomyelin synthase 2 is one of the determinants for plasma and liver sphingomyelin levels in mice.

BACKGROUND: It has been proposed that plasma sphingomyelin (SM) plays a very important role in plasma lipoprotein metabolism and atherosclerosis. Sphingomyelin synthase (SMS) is the last enzyme for SM de novo biosynthesis. Two SMS genes, SMS1 and SMS2, have been cloned and characterized. METHODS AND RESULTS: To evaluate the in vivo role of SMS2 in SM metabolism, we prepared SMS2 knockout (KO) and SMS2 liver-specific transgenic (LTg) mice and studied their plasma SM and lipoprotein metabolism. On a chow diet, SMS2 KO mice showed a significant decrease in plasma SM levels (25%, P<0.05), but no significant changes in total cholesterol, total phospholipids, or triglyceride, compared with wild-type (WT) littermates. On a high-fat diet, SMS2 KO mice showed a decrease in plasma SM levels (28%, P<0.01), whereas SMS2LTg mice showed a significant increase in those levels (29%, P<0.05), but no significant changes in other lipids, compared with WT littermates. Atherogenic lipoproteins from SMS2LTg mice displayed a significantly stronger tendency toward aggregation after mammalian sphingomyelinase treatment, compared with controls. Moreover, SMS2 deficiency significantly increased plasma apoE levels (2.0-fold, P<0.001), whereas liver-specific SMS2 overexpression significantly decreased those levels (1.8-fold, P<0.01). Finally, SMS2 KO mouse plasma promoted cholesterol efflux from macrophages, whereas SMS2LTg mouse plasma prevented it. CONCLUSIONS: We therefore believe that regulation of liver SMS2 activity could become a promising treatment for atherosclerosis.

Pubmed ID: 19286635


  • Liu J
  • Zhang H
  • Li Z
  • Hailemariam TK
  • Chakraborty M
  • Jiang K
  • Qiu D
  • Bui HH
  • Peake DA
  • Kuo MS
  • Wadgaonkar R
  • Cao G
  • Jiang XC


Arteriosclerosis, thrombosis, and vascular biology

Publication Data

June 21, 2009

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL-64735
  • Agency: NHLBI NIH HHS, Id: HL-69817
  • Agency: NHLBI NIH HHS, Id: R01 HL064735
  • Agency: NHLBI NIH HHS, Id: R01 HL064735-01A1
  • Agency: NHLBI NIH HHS, Id: R01 HL093419
  • Agency: NHLBI NIH HHS, Id: R01 HL093419-01A1

Mesh Terms

  • Animals
  • Apolipoproteins E
  • Atherosclerosis
  • Biological Transport
  • Cells, Cultured
  • Cholesterol
  • Dietary Fats
  • Humans
  • Lipoproteins
  • Liver
  • Macrophages
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Sphingomyelin Phosphodiesterase
  • Sphingomyelins
  • Transferases (Other Substituted Phosphate Groups)