The Role Of LXRα On Homocysteine Induced Atherosclerosis

Objective To investigate the influence of homocysteine(Hcy)on the expression of Liver X repceptor α(LXRα)and its role in foam cell formation and atherosclerosis.Methods Apo E-/-and C57BL/6J mice were fed a normal chow diet without or with methionine supplementation.Mice were sacrificed after 20 weeks for the measurement of plasma Hcy and lipid profiles.The aortic root was obtained for the examination of atheroslcerosis lesions and expression of LXRα.THP-1 monocytes were cultured and induced by PMA and oxidized low density lipoprotein(ox-LDL)to form foam cells.Then cells were intervened by and different concentrations of homocysteine(Hcy)for 24 hours.Oil red O staining was performed for identification and qualitative analysis.The protein expression of LXRα and its target gene ABCG1 as well as ABCA1 was detected by cyto-immunofluorescence and Western blot.Results Plasma Hcy levels were significantly elevated in groups supplemented with methionine while lipid profiles were not influenced.Hhcy could accelerate the atherosclerosis lesions formation and decrease the expression of LXRα.Oil red O staining showed that Hcy facilitated foam cell formation.The immunofluorescence and Western blot results showed that the expression of LXRα,ABCG1 and ABCA1 protein were decreased after the intervention of Hcy.Conclusions Hcy could promote the formation of foam cells and accelerate the atheroslcerosis lesions formation via down-regulating the expression of LXRα,ABCG1 and ABCA1 protein.