Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming
| Autor: | Samuel D. Wright, Niklas Bode, Alena Grebe, Thomas Ulas, Anja Kerksiek, Jan-Åke Gustafsson, Terje Espevik, Victoria Hawxhurst, Ingemar Björkhem, Chris Hempel, Larisa I. Labzin, Marit Westerterp, Siril Skaret Bakke, Joachim L. Schultze, Jonel Trebicka, Sebastian Zimmer, Georg Nickenig, Mona Skjelland, Dominic De Nardo, Bente Halvorsen, Michael T. Heneka, Dieter Lütjohann, Eicke Latz, Alan R. Tall, Michael L. Fitzgerald |
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| Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Translational Immunology Groningen (TRIGR) |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Apolipoprotein B Plaque Atherosclerotic/drug therapy pathology [Atherosclerosis] Gene Expression Regulation/drug effects Beta-Cyclodextrins drug effects [Gene Expression Regulation] 030204 cardiovascular system & hematology Pharmacology Cardiovascular System Cholesterol/metabolism chemistry.chemical_compound Mice Endocrinology Macrophages/drug effects 0302 clinical medicine Macrophage Plaque Liver X Receptors beta-Cyclodextrins/pharmacology drug effects [Macrophages] metabolism [Liver X Receptors] biology pharmacology [beta-Cyclodextrins] Reverse cholesterol transport beta-Cyclodextrins General Medicine Plaque Atherosclerotic 2-Hydroxypropyl-beta-cyclodextrin Cholesterol Cardiovascular Diseases Atherosclerotic/drug therapy lipids (amino acids peptides and proteins) ddc:500 Crystallization pathology [Plaque Atherosclerotic] Oxysterol therapeutic use [beta-Cyclodextrins] genetics [Atherosclerosis] Article drug therapy [Atherosclerosis] 03 medical and health sciences In vivo genetics [Plaque Atherosclerotic] Journal Article Animals Humans drug therapy [Plaque Atherosclerotic] Liver X receptor drug effects [Biological Transport] Liver X Receptors/metabolism Biological Transport/drug effects Macrophages Atherosclerosis/drug therapy Biological Transport metabolism [Cholesterol] Atherosclerosis 030104 developmental biology chemistry Gene Expression Regulation biology.protein metabolism [Macrophages] Sugars |
| Zdroj: | Zimmer, S, Grebe, A, Bakke, S S, Bode, N, Halvorsen, B, Ulas, T, Skjelland, M, De Nardo, D, Labzin, L I, Kerksiek, A, Hempel, C, Heneka, M T, Hawxhurst, V, Fitzgerald, M L, Trebicka, J, Björkhem, I, Gustafsson, J-Å, Westerterp, M, Tall, A R, Wright, S D, Espevik, T, Schultze, J L, Nickenig, G, Lütjohann, D & Latz, E 2016, ' Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming ', Science Translational Medicine, vol. 8, no. 333, pp. 333ra50 . https://doi.org/10.1126/scitranslmed.aad6100 Science translational medicine 8(333), 333ra50-333ra50 (2016). doi:10.1126/scitranslmed.aad6100 Science Translational Medicine, 8(333):333ra50. AMER ASSOC ADVANCEMENT SCIENCE Science Translational Medicine |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aad6100 |
| Popis: | Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B–containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)–mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis. This is a submitted manuscript of an article published by American Association for the Advancement of Science in Science Translational Medicine, 06 Apr 2016 |
| Databáze: | OpenAIRE |
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