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[Sphingomyelin synthase 2 deficiency decreases atherosclerosis and inhibits inflammation in mice.] [Ariticle in Chinese]

QIN Rui, CHEN Ming-Liang, ZHU Ke, DENG Jin-Bo, SHI Yuan-Yuan^*

Institute of Neurobiology, Medical College of Henan University, Kaifeng 475004, China

Abstract

Plasma sphingomyelin (SM) has been shown to be an independent risk factor for coronary heart disease, and sphingomyelinsynthase 2 (SMS2) contributes to de novo SM biosynthesis and plasma membrane SM levels. The aim of the present study is toevaluate the in vivo role of SMS2 deficiency in serum SM metabolism and atherosclerosis (AS) development. We used male SMS2knockout (SMS2-/-) and C57BL/6J (wild-type, WT) mice as experimental and control groups, respectively. Each group was fed high-fatdiet (1% cholesterol, 20% leaf fat), as well as bile salt for accelerating the atherosclerotic formation. After three months of feeding, themice were killed to observe aortic arches and oil red-stained longitudinal sections of thoracoabdominal aortae. Fasting blood sampleswere taken from the tail vein before and after high-fat diet, and the serum lipid and SM levels were measured by using kits and enzymaticmethod respectively. Western blot was used to analyze the contents of nuclear factor-κB (NFκB) p65 subunit in peritoneal macrophagesstimulated with lipopolysaccharide (LPS) after high-fat diet. The results showed that after high-fat diet, SMS2-/- mice presenteddecreased atherosclerotic lesions in aortic arch and thoracoabdominal aorta compared with WT mice. Regardless of whether high-fat dietwere given or not, SMS2-/- mice showed a significant decrease in serum SM level (P<0.05), but no significant changes in serum lipidlevels, compared with WT mice. The expressions of NFκB p65 were attenuated in macrophages from SMS2-/- mice in response to LPSstimulation compared with those of the WT mice. These results suggest that SMS2 deficiency decreases AS and inhibits inflammationin mice. Thus, SMS2 deficiency may be a potential therapeutic strategy.

Key words: sphingomyelin synthase 2; sphingomyelin; atherosclerosis; nuclear factor-κB

Received: 2010-05-05　　Accepted: 2010-06-29

Corresponding author: 石渊渊　　E-mail: syy5161@henu.edu.cn

Citing This Article：

QIN Rui, CHEN Ming-Liang, ZHU Ke, DENG Jin-Bo, SHI Yuan-Yuan. [Sphingomyelin synthase 2 deficiency decreases atherosclerosis and inhibits inflammation in mice.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (4): 333-338 (in Chinese with English abstract).