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.
OBJECTIVE: We examined the role of the CXCR2 ligand growth-related oncogene (GRO) alpha in humanatherosclerosis. 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.
Authors: David L Simpson; Nolan L Boyd; Sunjay Kaushal; Steve L Stice; Samuel C Dudley Journal: Biotechnol Bioeng Date: 2011-09-02 Impact factor: 4.530
Authors: Leticia Castillo; Anand Rohatgi; Colby R Ayers; Andrew W Owens; Sandeep R Das; Amit Khera; Darren K McGuire; James A de Lemos Journal: J Interferon Cytokine Res Date: 2010-05 Impact factor: 2.607
Authors: Peter S Munk; Unni M Breland; Pål Aukrust; Oyvind Skadberg; Thor Ueland; Alf I Larsen Journal: J Thromb Thrombolysis Date: 2011-01 Impact factor: 2.300