Global analysis of differentially expressed genes in oxidized LDL-treated human aortic smooth muscle cells

Abstract

Oxidized low density lipoproteins (OxLDL) play a key role in atherogenesis and induce a wide range of biological effects on smooth muscle cells. We used two commercially available cDNA microarray systems with a total of 35,932 human genes to determine differentially expressed genes in OxLDL-treated human aortic smooth muscle cells (HASMC) and to identify novel genes responsive to this agonist. We found a significant increase in expression of 180 and a significant decrease in expression of 192 named genes after treatment by OxLDL, compared with native LDL. Real time-PCR analysis confirmed microarray data for seven of eight tested genes. The differentially regulated genes were grouped into 16 classes based on the functions of the corresponding protein products. Our data demonstrate that OxLDL predominantly elevates expression of genes involved in cell–cell interactions, membrane transport, oncogenesis, apoptosis, and transcription and decreases expression of genes responsible for protein and nucleic acid biosynthesis, lipid metabolism, and humoral responses. Interestingly, we identify for the first time expression of metastasis-related protein (MB2) and novel scavenger receptor SREC-II in HASMC and these were upregulated 12- and 3-fold by OxLDL treatment, respectively. These findings have major implications for understanding atherogenic effect of OxLDL.