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- W130514544 abstract "TLR4 activation induces the expression of IL-6 which may initiate or aggravate atherosclerotic lesions. The purpose of this study was to test the hypothesis that TLR4 gene silencing may attenuate atherosclerosis progression through inhibiting the expression of IL-6 induced by endotoxin.TLR4 knockdown ECV304 cell line (ECV304-TLR4) was constructed and cells were divided into four groups: control group (with fresh serum-free medium in ECV304 cells), LPS group (with LPS in ECV304 cells), LPS + LY294002 group (pretreatment with LY294002 and then adding LPS in ECV304 cells) and LPS + RNAi group (treatment with LPS in ECV304-TLR4). Cells were collected and the protein expression of P-AKT, AKT, P65, Iκ-α and IL-6 were assayed. Fifty-four apoE−/− mice were equally divided into two groups: group 1 received adenoviral RNAi vector containing TLR4 and group 2 received adenoviral RNAi vector containing scrambled siRNA as a negative control at the end of week 6. All mice were fed a high-fat diet and received celiac injections of LPS (1mg/kg, twice per week) for 10 weeks and were then sacrificed. Levels of serum lipids and IL-6 were measured. Plaque contents were evaluated by immunohistochemistry and the vulnerability index (VI) was calculated as:VI = (macrophage + lipid)/(SMC + collagen) contents. The results showed that TLR4 protein expression in vitro was significantly inhibited in ECV304-TLR4. Compared with control cells (0.67 ± 0.002), the NF-κB binding activity reached the maximum at 30min stimulation of LPS (1.89 ± 0.04),which was inhibited by RNAi (0.96 ± 0.04) (P P 0.05). Plaque Area, lipid content and serum lipid levels between the two groups showed no significant difference. In conclusion, TLR4 gene silencing significantly reduces the expression of IL-6 and attenuates atherosclerosis progression probably through the inhibition of PI3-kinase/Akt/NF-κB signaling pathway." @default.
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- W130514544 date "2007-10-16" @default.
- W130514544 modified "2023-09-28" @default.
- W130514544 title "Abstract 309: TLR4 Gene Silencing Attenuates Atherosclerosis Progression via Inhibition of PI3-kinase/Akt/NF-κB Signaling Pathway in Apolipoprotein E Knockout Mice" @default.
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