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Global analysis of differentially expressed genes in oxidized LDL-treated human aortic smooth muscle cells
Sergiy Sukhanov1, Yao Hua Song, Patrick Delafontaine
1Division of Cardiovascular Diseases, Kansas University Medical center, 1001 Eaton Hall, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
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.
Insights
Oxidized low-density lipoproteins (OxLDL) alter gene expression in human aortic smooth muscle cells, impacting pathways crucial for atherogenesis. This study identifies novel OxLDL-responsive genes, including metastasis-related protein (MB2) and scavenger receptor SREC-II.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genomics
Background:
- Oxidized low-density lipoproteins (OxLDL) are implicated in the development of atherosclerosis.
- OxLDL exerts diverse biological effects on vascular smooth muscle cells, contributing to atherogenesis.
Purpose of the Study:
- To identify genes differentially expressed in human aortic smooth muscle cells (HASMC) upon treatment with OxLDL.
- To discover novel genes regulated by OxLDL in the context of atherogenesis.
Main Methods:
- Utilized two cDNA microarray systems analyzing 35,932 human genes.
- Confirmed microarray findings for selected genes using real-time PCR.
- Grouped differentially expressed genes into functional classes.
Main Results:
- OxLDL significantly altered the expression of 180 upregulated and 192 downregulated genes in HASMC.
- OxLDL predominantly increased genes involved in cell-cell interactions, membrane transport, oncogenesis, apoptosis, and transcription.
- OxLDL decreased genes related to protein/nucleic acid biosynthesis, lipid metabolism, and humoral responses.
- Identified upregulation of metastasis-related protein (MB2) and scavenger receptor SREC-II by OxLDL.
Conclusions:
- OxLDL significantly modulates gene expression in HASMC, affecting pathways critical to atherogenesis.
- The identification of novel OxLDL-responsive genes like MB2 and SREC-II provides new insights into OxLDL's role in cardiovascular disease.
- These findings enhance our understanding of the molecular mechanisms underlying OxLDL's atherogenic effects.