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.


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.
Levula
M
M
Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland. mari.levula@uta.fi
Jaakkola
O
O
Luomala
M
M
Nikkari
S T
ST
Lehtimäki
T
T
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D006133:Growth Substances / Q000235:genetics; D006487:Hemostasis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D006133:Growth Substances; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein