An Effect on Cholesterol Content in Foam Cells by Blocking the Extracellular Signal-regulated Kinase 1/2 Signal Pathway and the Nuclear Factor-κB Signal Pathway with Angiotensin-(1-7)
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    Abstract:

    AimTo invstigate the regulation of angiotensin-(1-7) (Ang(1-7)) to the expression of the activity of extracellular signal-regulated kinase-1/2 (ERK1/2) and the activity of nuclear factor-κB (NF-κB) in THP-1 derived-foam cells and to analyze the relationship between the ERK1/2 signal pathway and the NF-κB signal pathway.MethodsTo establish a macrophage-derived foam cell model of human monocylic THP-1 cell line, handle the cells in different conditions for 72 hours, which are divided into control group with medium added nothing, foam cell group, intervention fo-am cell groups advanced respectively by 10-6 mol/L Ang-(1-7), 10 μmol/L PD98059, 10 μmol/L TPCK (tosyl-phenylalanine chloromethyl-ketone), 10-6 mol/L Ang-(1-7)+10 μmol/L TPCK, 10-6 mol/L Ang-(1-7)+10 μmol/L PD98059.The differentiated cells were observed after oil red O staining under light microscope, high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (HPLC-MS) was used for quantitative analysis of cellular cholesterol, immunohistochemistry was employed to identify the expression of NF-κB in the differentiated cells, and the expression of p-ERK1/2 protection in the differentiated cells was detected by Western blotting.ResultsAng-(1-7) downregulated the expression of the activity of ERK1/2 and the activity of NF-κB (p<0.05), meanwhile, Ang-(1-7) downregulated the content of cholesterol in THP-1 derived foam cells (p<0.05), specific inhibitor PD98059 and specific inhibitor TPCK was used to reduce the content of total cholesterol in THP-1 derived foam cells (p<0.05), compared with povidone Ang-(1-7) and specific inhibitor PD98059 or specific inhibitor TPCK was proved to significantly decrease the content of total cholesterol in THP-1 derived foam cells (p<0.01).Specific inhibitor TPCK was used to abrogate phosphorylation of NF-κB for further evaluation (p<0.01), but didn't abrogate phosphorylation of ERK1/2 for further evaluation (p>0.05).Specific inhibitor PD98059 was used to abrogate phosphorylation of ERK1/2 and NF-κB for further evaluation (p<0.05).ConclusionsAng-(1-7) can lessen the content of cholesterol in THP-1 derived foam cells by decreasing the the activity of ERK1/2 and the activity of NF-κB.Specific inhibitor PD98059 and specific inhibitor TPCK is used to reduce the content of total cholesterol in THP-1 derived foam cells.ERK1/2 may be the upstream substance before NF-κB in the signaling pathway.

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LIU Juan, YANG Zhi-Ming, BIAN Yun-Fei,,YAN Feng. An Effect on Cholesterol Content in Foam Cells by Blocking the Extracellular Signal-regulated Kinase 1/2 Signal Pathway and the Nuclear Factor-κB Signal Pathway with Angiotensin-(1-7)[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2012,20(7):593-599.

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  • Received:November 22,2011
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