A potential role of the CXC chemokine GRO alpha in atherosclerosis and plaque destabilization - Downregulatory effects of statins

作者：Breland Unni M^*; Halvorsen Bente; Hol Johanna; Oie Erik; Paulsson Berne Gabrielle; Yndestad Arne; Smith Camilla; Otterdal Kari; Hedin Ulf; Waehre Torgun; Sandberg Wiggo J; Froland Stig S; Haraldsen Guttorm; Gullestad Lars; Damas Jan K; Hansson Goran K; Aukrust Pal

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2008, 28(5): 1005-1011.

DOI：10.1161/ATVBAHA.108.162305

• atherosclerosis
• chemokines
• inflammation
• endothelium

Objective-We examined the role of the CXCR2 ligand growth-related oncogene (GRO) alpha in human atherosclerosis.
Methods and Results-GRO alpha levels were examined by enzyme immunoassay, real-time quantitative RT-PCR, and cDNA microarrays. The in vitro effect of statins on GRO alpha was examined in endothelial cells and THP-1 macrophages. Our main findings were: (1) GRO alpha 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 GRO alpha comparing controls (n = 20). (3) We found increased expression of GRO alpha within symptomatic carotid plaques, located to macrophages and endothelial cells. (4) GRO alpha enhanced the release of matrix metalloproteinases in vascular smooth muscle cells, and increased the binding of acetylated LDL in macrophages. (5) Atorvastatin downregulated GRO alpha levels as shown both in vitro in endothelial cells and macrophages and in vivo in PBMCs from CAD patients. (6) The effect on GRO alpha in endothelial cells involved increased storage and reduced secretion of GRO alpha.
Conclusions-GRO alpha could be involved in atherogenesis and plaque destabilization, potentially contributing to inflammation, matrix degradation, and lipid accumulation within the atherosclerotic lesion.

• 出版日期2008-5