Open AccessA Potential Role of the CXC Chemokine GROα in Atherosclerosis and Plaque Destabilization
Author(s) -
Unni M. Breland,
Bente Halvorsen,
Johanna Hol,
Erik Øie,
Gabrielle Paulsson-Berne,
Arne Yndestad,
Camilla Smith,
Kari Otterdal,
Ulf Hedin,
Torgun Wæhre,
Wiggo J. Sandberg,
Stig S. Frøland,
Guttorm Haraldsen,
Lars Gullestad,
J Damås,
Göran K. Hansson,
Pål Aukrust
Publication year - 2008
Publication title -
arteriosclerosis, thrombosis, and vascular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.007
H-Index - 270
eISSN - 1524-4636
pISSN - 1079-5642
DOI - 10.1161/atvbaha.108.162305
Subject(s) - cxc chemokine receptors , chemokine , medicine , chemistry , chemokine receptor , inflammation
Objective— We examined the role of the CXCR2 ligand growth-related oncogene (GRO) α in human atherosclerosis.Methods and Results— GROα levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GROα was examined in endothelial cells and THP-1 macrophages. Our main findings were: (1) GROα 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 GROα comparing controls (n=20). (3) We found increased expression of GROα within symptomatic carotid plaques, located to macrophages and endothelial cells. (4) GROα enhanced the release of matrix metalloproteinases in vascular smooth muscle cells, and increased the binding of acetylated LDL in macrophages. (5) Atorvastatin downregulated GROα levels as shown both in vitro in endothelial cells and macrophages and in vivo in PBMCs from CAD patients. (6) The effect on GROα in endothelial cells involved increased storage and reduced secretion of GROα.Conclusions— GROα could be involved in atherogenesis and plaque destabilization, potentially contributing to inflammation, matrix degradation, and lipid accumulation within the atherosclerotic lesion.