Role of Suppressor of Cytokine Signaling-1 In Murine Atherosclerosis |
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| Authors: | Christina Grothusen Harald Schuett Anja Hillmer Stefan Lumpe Karsten Grote Matthias Ballmaier Andre Bleich Silke Glage Uwe J. F. Tietge Maren Luchtefeld Bernhard Schieffer |
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| Affiliation: | 1. Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.; 2. Department of Pediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany.; 3. Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.; 4. Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, The Netherlands.; University of Freiburg, Germany, |
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| Abstract: | BackgroundWhile the impact of inflammation as the substantial driving force of atherosclerosis has been investigated in detail throughout the years, the influence of negative regulators of pro-atherogenic pathways on plaque development has remained largely unknown. Suppressor of cytokine signaling (SOCS)-1 potently restricts transduction of various inflammatory signals and, thereby modulates T-cell development, macrophage activation and dendritic cell maturation. Its role in atherogenesis, however has not been elucidated so far.Methods and ResultsLoss of SOCS-1 in the low-density lipoprotein receptor deficient murine model of atherosclerosis resulted in a complex, systemic and ultimately lethal inflammation with increased generation of Ly-6Chi monocytes and activated macrophages. Even short-term exposure of these mice to high-cholesterol dieting caused enhanced atherosclerotic plaque development with accumulation of M1 macrophages, Ly-6C positive cells and neutrophils.ConclusionOur data not only imply that SOCS-1 is athero-protective but also emphasize the fundamental, regulatory importance of SOCS-1 in inflammation-prone organisms. |
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