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Sphingomyelin synthase 2 deficiency decreases atherosclerosis and inhibits inflammation in mice / 生理学报
Sheng Li Xue Bao ; (6): 333-338, 2010.
Article in Zh | WPRIM | ID: wpr-337742
Responsible library: WPRO
ABSTRACT
Plasma sphingomyelin (SM) has been shown to be an independent risk factor for coronary heart disease, and sphingomyelin synthase 2 (SMS2) contributes to de novo SM biosynthesis and plasma membrane SM levels. The aim of the present study is to evaluate the in vivo role of SMS2 deficiency in serum SM metabolism and atherosclerosis (AS) development. We used male SMS2 knockout (SMS2(-/-)) and C57BL/6J (wild-type, WT) mice as experimental and control groups, respectively. Each group was fed high-fat diet (1% cholesterol, 20% leaf fat), as well as bile salt for accelerating the atherosclerotic formation. After three months of feeding, the mice were killed to observe aortic arches and oil red-stained longitudinal sections of thoracoabdominal aortae. Fasting blood samples were taken from the tail vein before and after high-fat diet, and the serum lipid and SM levels were measured by using kits and enzymatic method respectively. Western blot was used to analyze the contents of nuclear factor-kappaB (NFkappaB) p65 subunit in peritoneal macrophages stimulated with lipopolysaccharide (LPS) after high-fat diet. The results showed that after high-fat diet, SMS2(-/-) mice presented decreased atherosclerotic lesions in aortic arch and thoracoabdominal aorta compared with WT mice. Regardless of whether high-fat diet were given or not, SMS2(-/-) mice showed a significant decrease in serum SM level (P<0.05), but no significant changes in serum lipid levels, compared with WT mice. The expressions of NFkappaB p65 were attenuated in macrophages from SMS2(-/-) mice in response to LPS stimulation compared with those of the WT mice. These results suggest that SMS2 deficiency decreases AS and inhibits inflammation in mice. Thus, SMS2 deficiency may be a potential therapeutic strategy.
Subject(s)
Full text: 1 Index: WPRIM Main subject: Aorta / Pathology / Sphingomyelins / Blood / Dietary Fats / NF-kappa B / Transferases (Other Substituted Phosphate Groups) / Mice, Knockout / Macrophages, Peritoneal / Atherosclerosis Type of study: Risk_factors_studies Limits: Animals Language: Zh Journal: Sheng Li Xue Bao Year: 2010 Type: Article
Full text: 1 Index: WPRIM Main subject: Aorta / Pathology / Sphingomyelins / Blood / Dietary Fats / NF-kappa B / Transferases (Other Substituted Phosphate Groups) / Mice, Knockout / Macrophages, Peritoneal / Atherosclerosis Type of study: Risk_factors_studies Limits: Animals Language: Zh Journal: Sheng Li Xue Bao Year: 2010 Type: Article