Department of Cardiology, First Affiliated Hospital, Jinan University, Guangzho, 510006, China; Department of Pharmacy, Zhongshan People's Hospital, Guangdong, Zhongshan, 528403, China.
Department of Laboratory Medicine, Zhongshan People's Hospital, Guangdong, Zhongshan, 528403, China.
Biochem Biophys Res Commun. 2020 Jul 30;528(3):440-446. doi: 10.1016/j.bbrc.2020.05.190. Epub 2020 Jun 4.
Previous studies have shown that the occurrence of atherosclerosis is closely related to changes of α2, 6-sialic 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 ApoEmice. 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.
先前的研究表明,动脉粥样硬化的发生与α2,6-唾液酸转移酶 I(ST6Gal-I)的变化密切相关。Bace1 已被确定为负责切割和分泌高尔基驻留 ST6Gal-I 的蛋白酶。只有少数尝试来阐明 Bace1 和动脉粥样硬化之间的直接联系。本研究的目的是探讨 Bace1 基因与动脉粥样硬化的关系。评估了高脂饮食喂养的 ApoE 小鼠中 Bace1 蛋白和 mRNA 的表达,并评估了高脂饮食喂养的 Bace1 小鼠中动脉粥样硬化的发展。在体外,在泡沫细胞模型中检测到 Bace1 基因的表达,并在 siRNA 敲低 Bace1 后检查泡沫细胞的形成。我们观察到 ApoE 小鼠动脉粥样硬化模型中主动脉根部 Bace1 表达显著增加。高脂组 Bace1 蛋白和 mRNA 水平表达显著增加。敲除 Bace1 基因后,血清脂质水平明显降低,内膜厚度明显变薄,与高脂饮食的野生型小鼠相比。泡沫细胞中 Bace1 蛋白和 mRNA 水平的表达显著升高。当用 siRNA 干扰敲低 Bace1 时,泡沫细胞的形成被阻断。我们的结果表明,升高的 Bace1 基因在动脉粥样硬化的进展中具有积极作用。影响糖基转移酶可能是其机制之一。