التفاصيل البيبلوغرافية
| العنوان: |
LXR agonist suppresses atherosclerotic lesion growth and promotes lesion regression in apoE*3Leiden mice: Time course and mechanisms |
| سنة النشر: |
2009 |
| مصطلحات موضوعية: |
chemokine receptor CCR7, Biomedical Research, fluorinated hydrocarbon, Cytoplasmic and Nuclear, cell receptor, cholesterol blood level, Apolipoprotein E3, cholesterol diet, Transgenic, Mice, Liver-X-receptor, Fluorinated, TO-901317, Receptors, animal, genetics, CD44, Hermes antigen, Sulfonamides, ABC transporter A1, disease course, Anticholesteremic Agents, lipoprotein, 2 trifluoro 1 hydroxy 1 (trifluoromethoxy)ethyl]phenyl]benzenesulfonamide, hypocholesterolemic agent, endothelial leukocyte adhesion molecule 1, Intercellular Adhesion Molecule-1, intercellular adhesion molecule 1, DNA-Binding Proteins, immunoglobulin enhancer binding protein, female, priority journal, Health, immunohistochemistry, monocyte, lipids (amino acids, peptides, and proteins), ABC transporter, triacylglycerol, E-Selectin, drug potency, liver X receptor, n (2, endothelium, Lipoproteins, animal experiment, macrophage, 2 trifluoroethyl) n [4 [2, remission, lipid, sulfonamide, drug mechanism, Animals, controlled study, ABCG1 protein, Antigens, protein expression, mouse, ABC transporter G1, Inflammation, Serum Amyloid A Protein, nonhuman, drug potentiation, Macrophages, animal model, 2 trifluoroethyl) n [4 (2, cholesterol, serum amyloid A, cell adhesion, Atherosclerosis, triacylglycerol blood level, DNA binding protein, Hydrocarbons, liver X receptor agonist, transgenic mouse, 2 trifluoro 1 hydroxy 1 trifluoromethylethyl)phenyl]benzenesulfonamide, apolipoprotein E3 (Leidein), pathology, ATP-Binding Cassette Transporters, cell adhesion molecule, metabolism |
| الوصف: |
The aim of this study was to define the anti-atherosclerotic role of liver-X-receptors (LXRs) under lesion progressive and lesion regressive conditions, to establish a temporal line of events, and to gain insights into the mechanisms underlying the anti-atherogenic potency of LXRs. We used apoE*3Leiden (E3L) mice to comprehensively and time-dependently dissect how T0901317, an LXR-agonist, inhibits initiation and progression of atherosclerotic lesions and regresses existing lipid- and macrophage-rich lesions. T0901317 suppresses lesion evolution and promotes lesion regression regarding lesion number, area, and severity. Quantitative plasma and vessel wall analyses corroborated by immunohistochemical evaluation of the aortic lesions revealed that under progressive (high-cholesterol diet) as well as regressive (cholesterol-free diet) conditions T0901317: i) significantly increases plasma triglyceride and total cholesterol levels; ii) does not affect the systemic inflammation marker, Serum amyloid A (SAA); iii) suppresses endothelial monocyte adhesion; and iv) induces the expression of the cholesterol efflux-related genes apolipoprotein E (apoE), ATP binding cassette (ABC) transporters ABCA1 and ABCG1. Furthermore, under progressive conditions, T0901317 suppresses the vascular inflammatory status (NF-κB) and the vascular expression of adhesion molecules [E-selectin, intercellular adhesion molecule (ICAM)-1, and CD44], lowers lesional macrophage accumulation, and blocks lesion evolution at the transition from lesional stage II to III. Under regressive conditions, T0901317 induces lesional macrophage disappearance and increases the expression of the chemokine receptor CCR7, a factor functionally required for regression. The LXR-agonist T0901317 retards vascular lesion development and promotes lesion regression at several levels. The findings support that vascular LXR is a potential anti-atherosclerotic target. Copyright © 2009 by the American Society for Biochemistry and Molecular Biology, Inc. |
| اللغة: |
English |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=dris___00893::e3a57a57fc2c8916cf249a1a57db3f97
http://resolver.tudelft.nl/uuid:5dd2c5ce-44a8-4ed8-9c64-481c6601a1f4 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.dris...00893..e3a57a57fc2c8916cf249a1a57db3f97 |
| قاعدة البيانات: |
OpenAIRE |