Increased APOE glycosylation plays a key role in the atherogenicity of L5 low-density lipoprotein

Liang Yin Ke, Hua Chen Chan, Chih Chieh Chen, Chuan Fa Chang, Po Liang Lu, Chih Sheng Chu, Wen Ter Lai, Shyi Jang Shin, Fu Tong Liu, Chu Huang Chen

研究成果: Article同行評審

13 引文 斯高帕斯(Scopus)


Low-density lipoprotein (LDL) is heterogeneous, composed of particles with variable atherogenicity. Electronegative L5 LDL exhibits atherogenic properties in vitro and in vivo, and its levels are elevated in patients with increased cardiovascular risk. Apolipoprotein E (APOE) content is increased in L5, but what role APOE plays in L5 function remains unclear. Here, we characterized the contributions of APOE posttranslational modification to L5’s atherogenicity. Using two-dimensional electrophoresis and liquid chromatography-mass spectrometry, we studied APOE’s posttranslational modification in L5 from human plasma. APOE structures with various glycan residues were predicted. Molecular docking and molecular dynamics simulation were performed to examine the functional changes of APOE resulting from glycosylation. We also examined the effects of L5 deglycosylation on endothelial cell apoptosis. The glycan sequence N-acetylgalactosamine, galactose, and sialic acid was consistently expressed on serine 94, threonine 194, and threonine 289 of APOE in L5 and was predicted to contribute to L5’s negative surface charge and hydrophilicity. The electrostatic force between the negatively charged sialic acid-containing glycan residue of APOE and positively charged amino acids at the receptor-binding area suggested that glycosylation interferes with APOE’s attraction to receptors, lipid-binding ability, and lipid transportation and metabolism functions. Importantly, L5 containing glycosylated APOE induced apoptosis in cultured endothelial cells through lectin-like oxidized LDL receptor-1 (LOX-1) signaling, and glycosylation removal from L5 attenuated L5-induced apoptosis. APOE glycosylation may contribute to the atherogenicity of L5 and be a useful biomarker for rapidly quantifying L5.

頁(從 - 到)9802-9813
期刊FASEB Journal
出版狀態Published - 2020 7月 1

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 生物化學
  • 分子生物學
  • 遺傳學


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