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Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex

  • Authors:
    • Ting Wang
    • Hang Ouyang
    • Hong Zhou
    • Longfei Xia
    • Xiaoyan Wang
  • View Affiliations / Copyright

    Affiliations: Jiangsu Key Laboratory of Medicine Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1955-1966
    |
    Published online on: August 2, 2018
       https://doi.org/10.3892/ijmm.2018.3805
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Abstract

A previous study has revealed that oxidized low‑density lipoprotein (oxLDL)/β2‑glycoprotein I (β2GPI)/anti‑β2‑glycoprotein I (anti‑β2GPI), an immune complex, is able to activate the Toll‑like receptor 4 (TLR4)/nuclear factor κβ (NF‑κβ) inflammatory signaling pathway in macrophages, and consequently enhance foam cell formation and the secretion of prothrombin activators. However, the effects of the oxLDL/β2GPI/anti‑β2GPI complex on vascular smooth muscle cells have yet to be investigated. The present study investigated whether the oxLDL/β2GPI/anti‑β2GPI complex was able to reinforce the pro‑atherogenic activities of a rat thoracic aorta smooth muscle cell line (A7r5) and examined the underlying molecular mechanisms. The results revealed that the oxLDL/β2GPI/anti‑β2GPI complex treatment significantly (P<0.05 vs. the media, oxLDL, oxLDL/β2GPI and β2GPI/anti‑β2GPI groups) enhanced the pro‑atherogenic activation of A7r5 cells, including intracellular lipid loading, Acyl‑coenzyme A cholesterol acyltransferase mRNA expression, migration, matrix metalloproteinase‑9 and monocyte chemoattractant protein 1 secretion, all via TLR4. In addition, the expression of TLR4 and the phosphorylation of NF‑κβ p65, p38 and ERK1/2 were also upregulated in oxLDL/β2GPI/anti‑β2GPI complex‑treated A7r5 cells. Pre‑treatment with TAK‑242, a TLR4 inhibitor, was able to partly attenuate the oxLDL/β2GPI/anti‑β2GPI complex‑induced phosphorylation of NF‑κβ p65; however, it had no effect on the phosphorylation of extracellular regulated kinase 1/2 (ERK1/2) and p38. Meanwhile, the NF‑κβ p65 inhibitor ammonium pyrrolidinedithiocarbamate and the ERK1/2 inhibitor U0126, but not the p38 inhibitor SB203580, were able to block oxLDL/β2GPI/anti‑β2GPI complex‑induced foam cell formation and migration in A7r5 cells. Hence, it was demonstrated that the oxLDL/β2GPI/anti‑β2GPI complex is able to enhance the lipid uptake, migration and active molecule secretion of A7r5 cells via TLR4, and finally deteriorate atherosclerosis plaques. Additionally, it was demonstrated that oxLDL/β2GPI/anti‑β2GPI complex‑induced foam cell formation and migration may be partly mediated by the TLR4/NF‑κβ signaling pathway and that ERK1/2 may also participate in the process.
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Copy and paste a formatted citation
Spandidos Publications style
Wang T, Ouyang H, Zhou H, Xia L and Wang X: Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex. Int J Mol Med 42: 1955-1966, 2018.
APA
Wang, T., Ouyang, H., Zhou, H., Xia, L., & Wang, X. (2018). Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex. International Journal of Molecular Medicine, 42, 1955-1966. https://doi.org/10.3892/ijmm.2018.3805
MLA
Wang, T., Ouyang, H., Zhou, H., Xia, L., Wang, X."Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex". International Journal of Molecular Medicine 42.4 (2018): 1955-1966.
Chicago
Wang, T., Ouyang, H., Zhou, H., Xia, L., Wang, X."Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex". International Journal of Molecular Medicine 42, no. 4 (2018): 1955-1966. https://doi.org/10.3892/ijmm.2018.3805
Copy and paste a formatted citation
x
Spandidos Publications style
Wang T, Ouyang H, Zhou H, Xia L and Wang X: Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex. Int J Mol Med 42: 1955-1966, 2018.
APA
Wang, T., Ouyang, H., Zhou, H., Xia, L., & Wang, X. (2018). Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex. International Journal of Molecular Medicine, 42, 1955-1966. https://doi.org/10.3892/ijmm.2018.3805
MLA
Wang, T., Ouyang, H., Zhou, H., Xia, L., Wang, X."Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex". International Journal of Molecular Medicine 42.4 (2018): 1955-1966.
Chicago
Wang, T., Ouyang, H., Zhou, H., Xia, L., Wang, X."Pro‑atherogenic activation of A7r5 cells induced by the oxLDL/β2GPI/anti‑β2GPI complex". International Journal of Molecular Medicine 42, no. 4 (2018): 1955-1966. https://doi.org/10.3892/ijmm.2018.3805
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