Research Article|Articles in Press

Serum amyloid A and interleukin -1β facilitate LDL transcytosis across endothelial cells and atherosclerosis via NF-κB/caveolin-1/cavin-1 pathway

  • Author Footnotes
    1 These authors contributed equally to this work.
    Xiong Jia
    1 These authors contributed equally to this work.
    Department of Cardiovascular Surgery, Jinan University 2nd Clinical Medicine College People's Hospital of Shenzhen, Shenzhen, Guangdong, 518020, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Zongtao Liu
    1 These authors contributed equally to this work.
    Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Department of Cardiovascular Surgery, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
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  • Yixuan Wang
    Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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  • Geng Li
    Corresponding author.
    Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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  • Xiangli Bai
    Corresponding author.
    Department of Laboratory Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China
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  • Author Footnotes
    1 These authors contributed equally to this work.


      • SAA and IL-1β increase the expression of cavin-1 and caveolin-1 via activation of NF-κB.
      • SAA and IL-1β promote LDL transcytosis across endothelial cells.
      • SAA and IL-1β accelerate the formation of atherosclerotic lesions.


      Background and aims

      Inflammatory molecules play important roles in atherosclerosis. We aimed to illustrate the roles of serum amyloid A (SAA), and interleukin (IL)-1β in low density lipoproteins (LDL) transcytosis and atherosclerosis.


      Effects of SAA and IL-1β on transcytosis of LDL were measured by an in vitro LDL transcytosis model. NF-κB/caveolin-1/cavin-1 pathway activation was investigated by Western blots and ELISA. Effects of SAA and IL-1β on the retention of LDL in aorta of C57BL/6J mice were detected by IVIS spectrum. Effects of SAA and IL-1β on atherosclerosis in Apoe−/− mice were examined by Oil Red O staining.


      SAA and IL-1β stimulated LDL transcytosis across endothelial cells (ECs), which was accompanied by an increase in LDL uptake by ECs. SAA and IL-1β enhanced the activity of nuclear factor (NF)-κB, consequently facilitating an up-regulation of proteins involved in caveolae formation, including caveolin-1 and cavin-1, along with an assembly of NLRP3 inflammasome. Furthermore, SAA- and IL-1β-induced effects were blocked by NF-κB subunit p65 siRNA. Meanwhile, SAA- and IL-1β-induced LDL transcytosis were effectively blocked by caveolin-1 siRNA or cavin-1 siRNA. Interestingly, SAA and IL-1β facilitated LDL entering into the aorta of C57BL/6J mice. In Apoe−/− mice, SAA and IL-1β increased the areas of lipid-rich atherosclerotic lesions in the both ascending and root of aorta. Furthermore, a significant increase in the NLRP3 inflammasome, accompanied by accumulation of cavin-1 and caveolin-1, was observed in the aortic endothelium of Apoe −/− mice.


      SAA and IL-1β accelerated LDL transcytosis via the NF-κB/caveolin-1/cavin-1 axis.

      Graphical abstract


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