Previous studies have shown that the occurrence of atherosclerosis is closely related to changes of a2, 6sialic acid transferase I (ST6Gal-I). Bace1 has been identified as a protease responsible for the cleavage and secretion of Golgi-resident ST6Gal-I. There have been only a few attempts to clarify the direct connection between Bace1 and atherosclerosis. The purpose of this study was to investigate the relationship between Bace1 gene and atherosclerosis. Expressions of Bace1 protein and mRNA in ApoE(-/-) mice fed on high-fat diet were evaluated and the development of atherosclerosis was assessed in Bace1(-/)- mice fed on high-fat diet. In vitro, the expression of Bace1 gene was detected in foam cell model and the formation of foam cells was examined after knocking down Bace1 by siRNA. We observed a significant increase in Bace1 expression in the aortic root in the model of atherosclerosis in ApoE(-/-) mice. The expression of Bace1 protein and mRNA levels had a remarkable increase in high-fat group. After knocking out the Bace1 gene, serum lipid levels were significantly lower and intimal thickness was obvious thinner than those in wild-type mice with high-fat diet. Expression of Bace1 protein and mRNA levels were significantly elevated in foam cell. The formation of foam cells was blocked when Bace1 was knocked down by siRNA interferes. Our results suggested that elevated Bace1 gene had a positive role in the progression of atherosclerosis. Affecting the glycosyltransferase may be one of its mechanisms. (C) 2020 Elsevier Inc. All rights reserved.