Comparison of Fibrate, Ezetimibe, Low- and High-Dose Statin Therapy for the Dyslipidemia of the Metabolic Syndrome in a Mouse Model

• Published in: Angiology 2011-02, Vol.62 (2), p.144-154
• Main Authors: Paraskevas, Kosmas I., Pantopoulou, Alkistis, Vlachos, Ioannis S., Agrogiannis, George, Iliopoulos, Dimitrios G., Karatzas, Gabriel, Tzivras, Dimitrios, Mikhailidis, Dimitri P., Perrea, Despina N.
• Format: Article
• Language: English
• Subjects: Animals; Atorvastatin Calcium; Azetidines - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Dyslipidemias - drug therapy; Dyslipidemias - etiology; Ezetimibe; Fenofibrate - therapeutic use; Heptanoic Acids - administration & dosage; Hypolipidemic Agents - administration & dosage; Male; Medical sciences; Metabolic Syndrome - complications; Metabolic Syndrome - drug therapy; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Pyrroles - administration & dosage
• ISSN: 0003-3197; 1940-1574
• DOI: 10.1177/0003319710387919

Background and Aim: The treatment-of-choice for the optimal management of the dyslipidemia of the metabolic syndrome (MetS) is not clearly defined. We compared the efficacy of 4 drug regimes for the management of this dyslipidemia in a mouse model. Materials and Methods: A total of 60 C57Bl6 mice comprised the study group. The first 10 received standard mouse food for the whole experiment (control group). The remaining 50 mice received atherogenic diet for 14 weeks until the development of the MetS. The mice were then divided into 5 groups: the 1st group continued receiving atherogenic diet, while the other 4 groups received atherogenic diet plus ezetimibe (10 mg/kg per day), fenofibrate (100 mg/kg per day), low-dose atorvastatin (10 mg/kg per day), or high-dose (40 mg/kg per day) atorvastatin, respectively, for another 8 weeks. Results: High-dose atorvastatin treatment achieved the best lipid profile compared with low-dose atorvastatin, ezetimibe, and fibrate therapy. The lipid profile of mice receiving atherogenic diet plus high-dose atorvastatin treatment was similar with mice on regular chow. Conclusions: High-dose atorvastatin treatment resulted in optimization of the lipid profile in the presence of a high-fat atherogenic diet in a mouse model. Our results suggest that high-dose atorvastatin treatment may be the optimal treatment option for the dyslipidemia associated with MetS. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.