Effects of oxidized low- and high-density lipoproteins on gene expression of human macrophages.

Objective: Oxidized low-density lipoprotein (ox-LDL) is a major factor in foam cell formation, whereas the role of oxidized high-density lipoprotein (ox-HDL) in this process is not known. The objective of the present study was to examine the effects of ox-LDL and ox-HDL on the gene expression of cultured human macrophages.

Material And Methods: Gene expression of human macrophages was studied after incubation for 1 day and 3 days with native and oxidized LDL and HDL using cDNA expression array. Expression of granulocyte-macrophage colony-stimulating factor 1, which was constantly up-regulated by ox-LDL and down-regulated by ox-HDL after 1- and 3 days of incubation in cDNA microarray experiments, was verified by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).

Results: Genes that showed altered expression were divided into six groups; 1) lipid metabolism, 2) inflammation, growth and hemostasis, 3) matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases, 4) enzymes, 5) structural and binding proteins and 6) annexins.

Conclusions: The microarray method was found to be applicable in analyzing changes in gene expression induced by oxidized lipoproteins in cultured human macrophages. Our results reflect different functional roles of ox-LDL and ox-HDL in foam cell formation.