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Transcriptional profiling of foam cells in response to hypercholesterolemia
Young-Hwa Goo1, Vijay K Yechoor2, Antoni Paul1
1Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, United States.
Insights
This study investigated how high cholesterol affects arterial foam cells in a mouse model. Researchers analyzed gene expression changes in foam cells exposed to varying cholesterol levels to understand their response in atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Macrophage Biology
Background:
- Hypercholesterolemia is a primary driver of atherosclerosis.
- Arterial macrophages (foam cells) accumulate cholesterol from lipoproteins.
- The impact of varying cholesterol levels on foam cell function is not well understood.
Purpose of the Study:
- To investigate the in vivo transcriptional response of foam cells to short- and long-term hypercholesterolemia.
- To understand macrophage plasticity within the atherosclerotic microenvironment.
Main Methods:
- Utilized apolipoprotein E-deficient mice, a model for atherosclerosis.
- Induced hypercholesterolemia via a western-type diet.
- Isolated foam cells from atherosclerotic lesions using laser capture microdissection.
- Analyzed gene expression using microarray and quantitative real-time PCR.
Main Results:
- Detailed the experimental setup for studying foam cell transcriptional changes.
- Provided methodology for RNA isolation, amplification, and analysis.
- Deposited microarray data in NCBI's Gene Expression Omnibus (GSE70619).
Conclusions:
- Established a framework for studying foam cell responses to cholesterol in vivo.
- Highlights the importance of studying macrophages in their native microenvironment.
- Provides valuable data for understanding the molecular mechanisms of atherosclerosis progression.
Abstract:
Hypercholesterolemia is a main risk factor for atherosclerosis development. Arterial macrophages, or foam cells, take-up and process lipoprotein particles deposited in arteries, and store much of the cholesterol carried by these particles in their cytoplasm. However, the effects of exposure to different cholesterol levels on foam cells remain poorly understood. Given the remarkable plasticity of macrophages in response to environmental variables, studies on macrophage biology should ideally be performed in the environment where they exert their physiological functions, namely atherosclerotic lesions in the case of foam cells. We used a mouse model of atherosclerosis, the apolipoprotein E-deficient mouse, to study in vivo the transcriptional response of foam cells to short- and long-term elevations in plasma cholesterol, induced by feeding mice a western type diet. The microarray data sets from this study have been deposited in NCBI's Gene Expression Omnibus under the accession number GSE70619. Here we provide detailed information on the experimental set-up, on the isolation of RNA by laser capture microdissection, and on the methodology used for RNA amplification and analysis by microarray and quantitative real-time PCR.
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