Lapaquistat acetate, a squalene synthase inhibitor, changes macrophage/lipid-rich coronary plaques of hypercholesterolaemic rabbits into fibrous lesions.
Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Young male WHHLMI rabbits were fed a diet supplemented with lapaquistat acetate (100 or 200 mg per kg body weight per day) for 32 weeks. Serum lipid levels were monitored every 4 weeks. After the treatment, lipoprotein lipid and coenzyme Q10 levels were assayed, and coronary atherosclerosis and xanthomas were examined histopathologically or immunohistochemically. From histopathological and immunohistochemical sections, the composition of the plaque was analysed quantitatively with computer-assisted image analysis. Xanthoma was evaluated grossly. KEY RESULTS: CONCLUSION AND IMPLICATIONS:
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Authors | M Shiomi, S Yamada, Y Amano, T Nishimoto, T Ito |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 154
Issue 5
Pg. 949-57
(Jul 2008)
ISSN: 0007-1188 [Print] England |
PMID | 18587443
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 1-((1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)acetyl)piperidine-4-acetic acid
- Apolipoprotein B-100
- Enzyme Inhibitors
- Hypolipidemic Agents
- Lipoproteins, LDL
- Oxazepines
- Piperidines
- Plasminogen Activator Inhibitor 1
- Triglycerides
- oxidized low density lipoprotein
- Ubiquinone
- Collagen
- Cholesterol
- Farnesyl-Diphosphate Farnesyltransferase
- Matrix Metalloproteinase 1
- coenzyme Q10
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Topics |
- Animals
- Apolipoprotein B-100
(blood)
- Cholesterol
(blood)
- Collagen
(metabolism)
- Coronary Artery Disease
(enzymology, etiology, pathology, prevention & control)
- Disease Models, Animal
- Disease Progression
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(blood, pharmacology)
- Farnesyl-Diphosphate Farnesyltransferase
(antagonists & inhibitors, metabolism)
- Hypercholesterolemia
(complications, drug therapy, enzymology, pathology)
- Hypolipidemic Agents
(blood, pharmacology)
- Image Interpretation, Computer-Assisted
- Immunohistochemistry
- Lipid Metabolism
(drug effects)
- Lipoproteins, LDL
(metabolism)
- Macrophages
(drug effects, pathology)
- Male
- Matrix Metalloproteinase 1
(metabolism)
- Oxazepines
(blood, pharmacology)
- Piperidines
(blood, pharmacology)
- Plasminogen Activator Inhibitor 1
(metabolism)
- Rabbits
- Triglycerides
(blood)
- Ubiquinone
(analogs & derivatives, metabolism)
- Xanthomatosis
(enzymology, etiology, pathology, prevention & control)
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