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Arterioscler Thromb Vasc Biol. 2008 May;28(5):1005-11. doi: 10.1161/ATVBAHA.108.162305. Epub 2008 Feb 14.

A potential role of the CXC chemokine GROalpha in atherosclerosis and plaque destabilization: downregulatory effects of statins.

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  • 1Research Institute for Internal Medicine, Rikshospitalet, University of Oslo, Norway. Unni.Mathilde.Breland@rr-research.no

Abstract

OBJECTIVE:

We examined the role of the CXCR2 ligand growth-related oncogene (GRO) alpha in human atherosclerosis.

METHODS AND RESULTS:

GROalpha levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GROalpha was examined in endothelial cells and THP-1 macrophages. Our main findings were: (1) GROalpha was among the 10 most differentially expressed transcripts comparing peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) and healthy controls. (2) Both patients with stable (n=41) and particularly those with unstable (n=47) angina had increased plasma levels of GROalpha comparing controls (n=20). (3) We found increased expression of GROalpha within symptomatic carotid plaques, located to macrophages and endothelial cells. (4) GROalpha enhanced the release of matrix metalloproteinases in vascular smooth muscle cells, and increased the binding of acetylated LDL in macrophages. (5) Atorvastatin downregulated GROalpha levels as shown both in vitro in endothelial cells and macrophages and in vivo in PBMCs from CAD patients. (6) The effect on GROalpha in endothelial cells involved increased storage and reduced secretion of GROalpha.

CONCLUSIONS:

GROalpha could be involved in atherogenesis and plaque destabilization, potentially contributing to inflammation, matrix degradation, and lipid accumulation within the atherosclerotic lesion.

PMID:
18276907
DOI:
10.1161/ATVBAHA.108.162305
[PubMed - indexed for MEDLINE]
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