Objective      To investigate the mechanism of the dysfunction of sterol regulatory element binding proteins cleavage-activating protein (SCAP)

induced by inflammation in the promotion of atheroma formation in ApoE

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mice.       Methods      A total of 24 male ApoE

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mice (C57BL/6 background

8 weeks old

weighting 18 to 24 g) were randomly divided into 2 groups

that is

high-sterol feeding group (H) and feeding+inflammation group (HC). Beside high fat diet feeding

the mice in the inflammation group were injected with 10% casein subcutaneously every other day

while those of control group were subjected to normal saline. After 14 weeks’ treatment

the serum inflammatory markers

serum amyloid A (SAA) and TNF-α were determined by ELISA

the lipid accumulation in the aorta was observed by HE and Oil Red O staining

the expression of low-density lipoprotein receptor (LDLr)

SCAP

α-mannosidases Ⅰ and Ⅱ were examined using real-time PCR and immunohistochemical assay.       Results      The level of SAA and TNF-α were dramatically higher in the serum of ApoE

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mice receiving subcutaneous injection of 10% casein (inflammation group) than control group (529±23 vs 248±27 ng/mL

37 900±3 100 vs 1 789±219 ng/mL

P0.01)

which indicated that the inflamed mice model was established successfully. The inflamed mice displayed more severe atheroma (P0.01)

and increased expression of LDLr

SCAP and α-mannosidaseⅡ at the mRNA (P0.05) and protein levels (P0.05) in the aorta

especially the active fragment NSREBP2 in the nucleus (P0.05) when compared with the mice in control group.       Conclusion      Inflammation enhances the expression of SCAP

and promotes SCAP glycosylation by up-regulating the expression of α-mannosidase Ⅱ in the aorta

and thus improves the atheroma formation in ApoE

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mice.