Format

Send to

Choose Destination
Arterioscler Thromb Vasc Biol. 2012 Dec;32(12):2910-8. doi: 10.1161/ATVBAHA.112.300383. Epub 2012 Oct 4.

Cholesterol accumulation regulates expression of macrophage proteins implicated in proteolysis and complement activation.

Author information

1
Department of Medicine, University of Washington, Seattle, WA 98109, USA

Abstract

OBJECTIVE:

Cholesterol accumulation by macrophages plays a key role in atherogenesis. To begin to develop a global picture of this process, we used proteomics and transcriptomics to analyze foam cells generated with acetyl-low-density lipoprotein, a classic ligand for scavenger receptors.

METHODS AND RESULTS:

Tandem mass spectrometry and stringent statistical analysis revealed that foam cells differentially expressed 15 of 542 proteins (2.8%) detected in macrophage-conditioned medium. Apolipoprotein E was one of the most upregulated proteins, confirming that proteins involved in lipid metabolism are important targets for regulation by sterol accumulation. However, levels of proteins linked to complement activation and lysosomal proteolysis also changed markedly. Transcriptional analysis demonstrated that 698 of 19,700 genes (3.5%) were regulated in foam cells, including many genes important in sterol metabolism. We also found that cholesterol accumulation regulated genes implicated in complement activation but failed to affect genes linked to proteolysis and macrophage polarization. Changes in protein levels in macrophage-conditioned medium were largely independent of changes in mRNA levels.

CONCLUSIONS:

Loading sterol into macrophages regulates levels of complement proteins and lysosomal proteases-key players in the immune system and plaque rupture. Posttranscriptional mechanisms are likely important for controlling levels of most of the proteins detected in macrophage medium.

PMID:
23042816
PMCID:
PMC3501207
DOI:
10.1161/ATVBAHA.112.300383
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center