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| Objectives: Oxidized low-density lipoprotein (oxLDL) is a proatherogenic lipoprotein, accumulating in the vascular wall and playing an important role in the development of atherosclerosis. This study aims to investigate the effect of berberine on HUVECs proliferation induced by oxLDL and its potential signaling pathways. Methods and results: HUVECs were stimulated with oxLDL and co-cultured with berberine at a variety of concentrations at different time points. The data showed that oxLDL (10-100 μg/ml) remarkably promoted HUVECs proliferation assessed by Cell Counting Kit-8 (CCK-8) and EdU assay. The effects were found to be involved in up-regulation of PCNA, NF-кB and LOX-1 and activation of PI3K/Akt, ERK1/2 and p38MAPK signaling pathways evaluated by either real time PCR or western blot analysis. Interestingly, HUVECs proliferation was significantly inhibited by berberine (5-25 μg/ml), which was associated with down-regulating of PCNA, NF-кB and LOX-1 and decreasing the phosphorylation of Akt, ERK1/2 and p38MAPK. Furthermore, the anti-proliferative effect of berberine on HUVECs was effectively abrogated by a PI3K inhibitor LY294002, an ERK1/2 inhibitor PD98059 and a p38 inhibitor SB202190 partly through the restoration of phosphorylation of Akt, ERK1/2 and p38MAPK. Conclusions: The data firstly demonstrated that berberine inhibited ox-LDL-induced HUVECs proliferation by decreasing the expression of PCNA, NF-кB and LOX-1 and suppressing the activation of PI3K/Akt, ERK1/2 and p38MAPK pathways, suggesting that berberine may be a potential candidate of medications to prevent the oxLDL-induced endothelial cells proliferation involved in endothelial dysfunction and atherosclerosis. |
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| Keywords:oxidized low-density lipoprotein; endothelial cell; proliferation; berberine; signal pathway |
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