High levels and inflammatory effects of soluble CXC ligand 16 (CXCL16) in coronary artery disease: down-regulatory effects of statins.
In: Cardiovascular research, Jg. 79 (2008-07-01), Heft 1, S. 195-203
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Zugriff:
Aims: CXC ligand 16 (CXCL16) may be involved in inflammation and lipid metabolism, and we hypothesized a role for this chemokine in coronary artery disease (CAD).
Methods and Results: We performed clinical studies in CAD patients as well as experimental studies in cells with relevance to atherogenesis [i.e. endothelial cells, vascular smooth muscle cells (SMC), and peripheral blood mononuclear cells (PBMC)]. We also examined the ability of HMG-CoA reductase inhibitors (statins) to modulate CXCL16 levels both in vivo and in vitro. Our main findings were: (i) patients with stable (n = 40) and unstable (n = 40) angina had elevated plasma levels of CXCL16 compared with controls (n = 20); (ii) low-dose simvastatin (20 mg qd, n = 15) and high-dose atorvastatin (80 mg qd, n = 9) down-regulated plasma levels of CXCL16 during 6 months of therapy; (iii) in vitro, atorvastatin significantly decreased the interleukin (IL)-1beta-mediated release of CXCL16 from PBMC and endothelial cells; (iv) attenuating effect of atorvastatin on the IL-1beta-mediated release of CXCL16 in PBMC seems to involve post-transcriptional modulation as well as down-regulation of CXCL16 release through inhibition of the protease a disintegrin and metalloproteinase 10 (ADAM10); (v) soluble CXCL16 increased the release of IL-8, monocyte chemoattractant peptide 1, and matrix metalloproteinases in vascular SMC and increased the release of IL-8 and monocyte chemoattractant peptide 1 in PBMC, with particularly enhancing effects in cells from CAD patients.
Conclusion: Our findings suggest that soluble CXCL16 could be linked to atherogenesis not only as a marker of inflammation, but also as a potential inflammatory mediator.
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High levels and inflammatory effects of soluble CXC ligand 16 (CXCL16) in coronary artery disease: down-regulatory effects of statins.
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Autor/in / Beteiligte Person: | Smith, C ; Halvorsen, B ; Otterdal, K ; Waehre, T ; Yndestad, A ; Fevang, B ; Sandberg, WJ ; Breland, UM ; Frøland, SS ; Oie, E ; Gullestad, L ; Damås, JK ; Aukrust, P |
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Zeitschrift: | Cardiovascular research, Jg. 79 (2008-07-01), Heft 1, S. 195-203 |
Veröffentlichung: | 2008- : Oxford : Oxford Journals ; <i>Original Publication</i>: London, British Medical Assn., 2008 |
Medientyp: | academicJournal |
ISSN: | 0008-6363 (print) |
DOI: | 10.1093/cvr/cvn071 |
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