The Probable Mechanisms Of LDL Oxidation Mediated By Vascular Cells

Atherosclerosis has been reported to be related with the level of plasma low-density lipoproteins (LDL). Once LDL was oxidized, its atherogenic effects developed. Researches demonstrated that vascular cells including macrosphages, endothelial cells and smooth muscle cells were able to oxidize low-density lipoprotein in vitro. LDL oxidation might be mediated by various oxidants generated by myeloperoxidase. To study the signaling pathway involved in cell-mediated oxidation, we observed the molecular mechanisms of LDL oxidation by using gene chip technology. This study include the following two aspects:1. LDL was cocultured with human THP-1 monocytes and endothelial cells separately for different times and LDL oxidation levels were examined.The results showed that LDL oxidation increased with the time of coculture by detecting the formation of diene or MDA and oxidation style of cells were different. As can be seen from Table 1 and 2, LDL oxidation level mediated by human THP-1 monocytes reached peak value at nine hours, but that mediated by endothelial cells delayed to twenty hours. For the sake of understanding LDL oxidation in two types of cells, we constructed to incubation time with the dispatch between Exp and control group about LDL oxidation level in these cells. From Figure 1 and 2, we could know that level of cell-mediated LDL oxidation elevated with the incubation time and reached a peak at nine hours, and twenty hours respectively. Oxidation capacity between these two types of cells was different and THP-1 had stronger ability. The incubation time also could affect LDL oxidation.2. Human THP-1 monocytes and endothelial cells were treated with LDL for nine hours and for twenty hours invidually. Microarray analysis on human signal transduction associated genes was profiled to determine changes in gene expression of two types of cells induced by LDL.From figures scanned for hybridization (Fig3,5) and scatter plot of normalized intensity data from microarray experiments (Fig4,6), we could see that many genes were differently expressed between Exp and control group. As for THP-1 monocytes, in 1,650 genes detected, thirteen genes were identified to be >two-fold difference in expression, among which nine genes with elevated expression and four genes with reduced expression. However, for endothelial cells, there were fifty-two genes different in expression: twenty-three genes expression elevated and twenty-nine genes expression reduced. We speculated that LDL oxidation mechanisms between these two types of cells were different.Conclusion: Oxidation capacity between these two types of cells was different and macrophages had stronger ability. The incubation time also could affect LDL oxidation. The mechanisms of LDL oxidation mediated by these two types of cells were different.