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Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques
- Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques
- Jang M.K.; Kim J.Y.; Jeoung N.H.; Kang M.A.; Choi M.-S.; Oh G.T.; Nam K.T.; Lee W.-H.; Park Y.B.
- Ewha Authors
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- Biochemical and Biophysical Research Communications
- Biochemical and Biophysical Research Communications vol. 323, no. 3, pp. 898 - 905
- SCIE; SCOPUS
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- Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor γ (PPARγ). Introduction of an endogenous PPARγ ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARγ. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARγ, which may be further related to the atherogenesis. © 2004 Elsevier Inc. All rights reserved.
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