| The roport show that sphingomyelion(SM) is gathered in atherosclerosis(AS) plaue. Plasma SM has been shown to be an independent risk factor for coronary heart disease. We found that plasma SM levels in apoE KO mice are 4-fold higher than in wild type mice. Inhibited SM synthesis can obvious inhibit the occurrence of AS in ApoE KO mice. Brand et al useα-P65mAb (a new type of mouse monoclonal antibody) first test that AS lesions have activated nuclear factorκB (NFκB), which were significantly higher than normal tissues.Thus AS which is characterized of chronic inflammation and proliferation process may be a typical example of chronic inflammation of cases by NFκB-mediated. Luberto et al [5] found that D609 (pharmacology inhibitor of SMS) can restraint NFκB of activation which was induced by TNF or LPS. These studies have shown that SM plays a very important role in AS. Inhibited SM synthesis may affect the activation of NFκB, thereby affecting the occurrence of AS.In order to study the relationship between SM and AS,we bring in 3 SMS2(+/-) mice(two female,one male)from State University of New York of America.We identified SMS2(-/-) mice by PCR.We use SMS2(-/-) mice as research object to discuss the mechanism of AS by SM for providing a theoretical basis of the clinical treatment and prevention of AS.Objective: 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.The effects of SMS2 deficiency on the development of atherosclerosis are investigated.Methods: We identified SMS2(-/-) mice by PCR.Then we used 3-months-old male SMS2(-/-) mice as experimental group and 3-months-old male wild-type mice(C57BL/6J) as control group.After 3 months of high-fat diet and high-cholesterol diet, The aortic arch of mice were exposed.The en face of mice were splitted and stained with oil red.The levels of serum HDL-c,LDL-c,CHO,TG and SM were measured. Peritoneal macrophage cells were collected from SMS2(-/-)and WT mice.Then they were stimulated with lipopolysaccharide(LPS).Nuclei were extracted from macrophage in order to measure NFκB activation by Western Blotting.Results: SMS2(-/-) mice showed decreased atherosclerotic lesions in the aortic arch and the en face compared with WT after 3 month on high-fat diet and high-cholesterol diet. On a chow diet, SMS2 KO mice showed a significant decrease in serum SM levels (p<0.05), but no significant changes in HDL-c,LDL-c,CHO,TG, compared with wild-type (WT) littermates. On a high-fat diet and high-cholesterol diet, SMS2 KO mice showed a decrease in serum SM levels (p<0.05), but no significant changes in other lipids, compared with WT littermates. NFκB activation were attenuated in macrophage from SMS2(-/-) mice.Conclusion:1.AS gene knockout animal models: the SMS2(-/-) mice which we have bred can be used as an ideal animal model of AS research.2. the relationship between SMS2 and SM metabolism: SMS2 is One of the determinants for plasma SM levels in mice.3. the relationship between SMS2 metabolism and AS: SMS2 deficiency in the macrophages reduces atherosclerosis in mice. Macrophage SMS2 is thus a potential therapeutic target for treatment of this disease.4. the relationship between SMS2 and fat:SMS2 may control weight.5. SMS2 is a modulator of NFκB activation, and thus it could play an important role in NFκB -mediated proatherogenic process.
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