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The Effects Of Ox-LDL In Human Atherosclerosis May Be Mediated In Part Via The TLR4 Pathway

Posted on:2007-01-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:H L GengFull Text:PDF
GTID:1104360185957117Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
To explore the immune mechanisms of atherosclerosis, we focus on the relationship between the effects of ox-LDL in human atherosclerosis and Toll-like receptor 4(TLR4). First, we detected the positive rates of serum autoantibodies associated with coronary arteriosclerosis, and then we measured the expression of TLR4 by using the flow cytometry and the real-time quantitative RT-PCR method. Through in vitro cell culture, we verified the effects of ox-LDL on the expression of TLR4, NF-κB activity and the release of MCP-1 and IL-8. To prove the associated of ox-LDL and TLR4, we detected the biological activities changing of ox-LDL after the expression of TLR4 was inhibited through RNA interference. Our study showed that the positive rates of serum anti-ox-LDL in CAD group were significantly higher than that in control, and the expression level of TLR4 on peripheral-blood mononuclear cells was increased in atherosclerotic, but the differential expression of TLR4 has no correlation with the level of plasma lipids. Stimulation of ox-LDL could induce TLR4 expression in monocyte cell line. The NF-kappa B activity and the secretion of MCP-1 and IL-8 were enhanced by ox-LDL. Inhibition of TLR4 expression by using siRNA could attenuate the biological effects of ox-LDL.
Keywords/Search Tags:atherosclerosis, autoantibodies, oxidized LDL, Toll like receptor, reverse transcription-polymerase chain reaction, nuclear factor kappa B, interleukin-8, monocyte chemoattractant protein-1, small interference RNA
PDF Full Text Request
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