Abstract:
BACKGROUND:BMP4, a member of the transforming growth factor-beta superfamily, is upregulated in the aortas of diabetic db/db mice. However, little is known about its role in diabetic atherosclerosis. Therefore, we examined the roles of BMP4 in the formation of diabetic atherosclerosis in apolipoprotein E knockout (ApoE KO) mice and in the uptake of oxidized low density lipoprotein (oxLDL) in peritoneal macrophages of wild-type mice. METHODS:To induce diabetes, ApoE KO mice were intraperitoneally injected with streptozotocin. Diabetic and non-diabetic ApoE KO mice were then fed a high-fat diet for 4 weeks. Next, to investigate a role of BMP4 in the peritoneal macrophages, we examined the uptake of oxLDL in BMP4-treated macrophages. RESULTS:Diabetic ApoE KO mice showed accelerated progression of aortic plaques accompanied by increased luminal plaque area. Western blot analysis showed that BMP4 expression in the whole aorta was greatly increased in diabetic ApoE KO mice, than non-diabetic mice. Western blot analysis showed that the BMP4/SMAD1/5/8 signaling pathway was strongly activated in the aorta from diabetic ApoE KO mice, compared with control ApoE KO mice. Double immunofluorescence staining showed that BMP4 was expressed in MOMA2-labeled macrophage in the aortic lesions of ApoE KO mice. BMP4 significantly increased the uptake of oxLDL into peritoneal macrophages in vitro. CONCLUSION:We show that in the aorta of diabetic ApoE KO mice, BMP4 is increased and activates SMAD1/5/8. Our in vitro findings indicate that BMP4 enhances oxLDL uptake in mouse peritoneal macrophages, suggesting BMP4 may be involved in aortic plaque formation in diabetic ApoE KO mice. Targeting BMP4 may offer a new strategy for inhibition of plaque progression and stabilization of atherosclerotic lesions.
journal_name
J Inflamm (Lond)journal_title
Journal of inflammation (London, England)authors
Koga M,Yamauchi A,Kanaoka Y,Jige R,Tsukamoto A,Teshima N,Nishioku T,Kataoka Ydoi
10.1186/1476-9255-10-32subject
Has Abstractpub_date
2013-10-09 00:00:00pages
32issue
1issn
1476-9255pii
1476-9255-10-32journal_volume
10pub_type
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journal_title:Journal of inflammation (London, England)
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journal_title:Journal of inflammation (London, England)
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journal_title:Journal of inflammation (London, England)
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pub_type: 杂志文章,评审
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journal_title:Journal of inflammation (London, England)
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2016-09-13 00:00:00