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Status |
Public on Jul 01, 2017 |
Title |
Cyclodextrin treatment leads to atherosclerosis regression by dissolution of cholesterol crystals and LXR activation |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol levels. Since cholesterol retention and cholesterol crystals in arterial walls are key pathogenetic factors for atherogenesis, we assessed the therapeutic potential of increasing cholesterol solubility in vivo. Here we show that treatment of murine atherosclerosis with the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that solubilizes lipophilic substances, reduced atherosclerotic plaque size, cholesterol crystal (CC) load and promoted plaque regression even under continuing Western diet. CD solubilized CC and promoted cholesterylester and oxysterol production in macrophages leading to liver X receptor-mediated transcriptional reprogramming with increased cholesterol efflux and decreased inflammation. CD treatment may thus be used to increase cholesterol solubility and clearance to prevent or treat atherosclerosis.
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Overall design |
Bone marrow-derived macrophages (BMDMs) were derived from bone marrow isolated from tibiae and femurs of LXR -/- -/- mice on a C57BL/6 background and age matched littermate wild type mice. Bone marrow cells were cultured in DMEM supplemented with 10 % FCS, 10 g/ ml Ciprobay-500 and 40 ng/ ml M-CSF (R&D Systems) for six days. BMDMs were treated for 3h with 200 ug cholesterol crystals per 1 mio. cells or control medium. Subsequently cells were incubated for 6h with 10 mM CD before cell lysis in Trizol (Invitrogen). Samples were stored at -80 C for RNA isolation.
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Contributor(s) |
Zimmer S, Grebe A, Bode N, De Nardo D, Labzin L, Hempel C, Kerksiek T, Heneka M, Ulas T, Schultze J, Nickenig G, Lütjohann D, Latz E |
Citation(s) |
27053774 |
Submission date |
Jun 06, 2013 |
Last update date |
Jan 16, 2019 |
Contact name |
Joachim Schultze |
E-mail(s) |
j.schultze@uni-bonn.de
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Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
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Department |
Genomics and Immunoregulation
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Street address |
Carl-Troll-Strasse 31
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City |
Bonn |
State/province |
NRW |
ZIP/Postal code |
53115 |
Country |
Germany |
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Platforms (1) |
GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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Samples (20)
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Relations |
BioProject |
PRJNA207331 |