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The aim of this study was to evaluate the effects ofTannerella forsythiaand its major surface virulence factor, BspA, on the progression of atherosclerosis in ApoE−/− mice and the expression of lipid metabolism-related genes.PMA-differentiated THP-1 cells were treated with BspA to detect foam cell formation. The proximal aortas of ApoE−/− mice injected withT. forsythiaor BspA were stained with oil red O to examine lipid deposition. The serum levels of CRP, HDL, and LDL were detected by ELISA. The liver tissue ofT. forsythia- or BspA-injected ApoE−/− mice was examined for mRNA expression of lipid metabolism-related genes, such as liver X receptors (LXRαandLXRβ) and ATP-binding cassette transporter A1 (ABCA1).Tannerella forsythiaand BspA induced foam cell formation in THP-1 cells and accelerated the progression of atherosclerotic lesions in ApoE−/− mice. Mouse serum levels of CRP and LDL were increased, and HDL was decreased byT. forsythiaand BspA. The expression levels ofLXRαandLXRβ, andABCA1in liver tissue were decreased byT. forsythiaand BspA.Tannerella forsythiaand BspA augmented atherosclerotic lesion progression in ApoE−/− mice. This process may be associated with downregulation of lipid metabolism-related gene expression.