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Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex

A previous study has revealed that oxidized low-density lipoprotein (oxLDL)/β(2)-glycoprotein I (β(2)GPI)/anti-β(2)-glycoprotein I (anti-β(2)GPI), an immune complex, is able to activate the Toll-like receptor 4 (TLR4)/nuclear factor κβ (NF-κβ) inflammatory signaling pathway in macrophages, and conse...

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Autores principales: Wang, Ting, Ouyang, Hang, Zhou, Hong, Xia, Longfei, Wang, Xiaoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108850/
https://www.ncbi.nlm.nih.gov/pubmed/30085340
http://dx.doi.org/10.3892/ijmm.2018.3805
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author Wang, Ting
Ouyang, Hang
Zhou, Hong
Xia, Longfei
Wang, Xiaoyan
Wang, Ting
author_facet Wang, Ting
Ouyang, Hang
Zhou, Hong
Xia, Longfei
Wang, Xiaoyan
Wang, Ting
author_sort Wang, Ting
collection PubMed
description A previous study has revealed that oxidized low-density lipoprotein (oxLDL)/β(2)-glycoprotein I (β(2)GPI)/anti-β(2)-glycoprotein I (anti-β(2)GPI), 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/β(2)GPI/anti-β(2)GPI complex on vascular smooth muscle cells have yet to be investigated. The present study investigated whether the oxLDL/β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI complex treatment significantly (P<0.05 vs. the media, oxLDL, oxLDL/β(2)GPI and β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI complex-treated A7r5 cells. Pre-treatment with TAK-242, a TLR4 inhibitor, was able to partly attenuate the oxLDL/β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI complex-induced foam cell formation and migration in A7r5 cells. Hence, it was demonstrated that the oxLDL/β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI 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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spelling pubmed-61088502018-08-27 Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex Wang, Ting Ouyang, Hang Zhou, Hong Xia, Longfei Wang, Xiaoyan Wang, Ting Int J Mol Med Articles A previous study has revealed that oxidized low-density lipoprotein (oxLDL)/β(2)-glycoprotein I (β(2)GPI)/anti-β(2)-glycoprotein I (anti-β(2)GPI), 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/β(2)GPI/anti-β(2)GPI complex on vascular smooth muscle cells have yet to be investigated. The present study investigated whether the oxLDL/β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI complex treatment significantly (P<0.05 vs. the media, oxLDL, oxLDL/β(2)GPI and β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI complex-treated A7r5 cells. Pre-treatment with TAK-242, a TLR4 inhibitor, was able to partly attenuate the oxLDL/β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI complex-induced foam cell formation and migration in A7r5 cells. Hence, it was demonstrated that the oxLDL/β(2)GPI/anti-β(2)GPI 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/β(2)GPI/anti-β(2)GPI 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. D.A. Spandidos 2018-10 2018-08-02 /pmc/articles/PMC6108850/ /pubmed/30085340 http://dx.doi.org/10.3892/ijmm.2018.3805 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Ting
Ouyang, Hang
Zhou, Hong
Xia, Longfei
Wang, Xiaoyan
Wang, Ting
Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex
title Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex
title_full Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex
title_fullStr Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex
title_full_unstemmed Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex
title_short Pro-atherogenic activation of A7r5 cells induced by the oxLDL/β(2)GPI/anti-β(2)GPI complex
title_sort pro-atherogenic activation of a7r5 cells induced by the oxldl/β(2)gpi/anti-β(2)gpi complex
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108850/
https://www.ncbi.nlm.nih.gov/pubmed/30085340
http://dx.doi.org/10.3892/ijmm.2018.3805
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