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

Abstract

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.

• Atherosclerosis
• foam cell
• microarray
• ox‐HDL
• ox‐LDL

Acknowledgements

This study was funded by the Academy of Finland (grant no. 104821), the Emil Aaltonen Foundation, the Medical Research Foundation of Tampere University Hospital and the Finnish Foundation for Cardiovascular Research. We thank Shahenuul Islam, MD, for help with the statistical analyses and technicians Ulla Saarijoki and Marita Koli for their skillful advice.