Inhibitory effect of co-administration of atorvastatin and endothelin-1 receptor antagonist on the progression of atherosclerosis in rabbit
Autor: | Jinwen Liu, Bo Yang, Dong Wang, Tiande Li, Yu Sun, Xiaoyong Sai, Rongbin Zhou |
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Rok vydání: | 2013 |
Předmět: |
Microbiology (medical)
Male medicine.medical_specialty Normal diet medicine.drug_class Endothelin A Receptor Antagonists Atorvastatin Blood lipids Down-Regulation Diet High-Fat Iliac Artery Pathology and Forensic Medicine Proinflammatory cytokine New Zealand white rabbit Internal medicine medicine Immunology and Allergy Animals Pyrroles Aorta Abdominal RNA Messenger biology Endothelin-1 Phenylpropionates business.industry Antagonist NF-kappa B Drug Synergism General Medicine Receptor antagonist biology.organism_classification Atherosclerosis Lipids Plaque Atherosclerotic Disease Models Animal Endocrinology Pyrimidines Matrix Metalloproteinase 9 Heptanoic Acids Disease Progression Darusentan Drug Therapy Combination Rabbits Hydroxymethylglutaryl-CoA Reductase Inhibitors Inflammation Mediators business medicine.drug |
Zdroj: | APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 122(6) |
ISSN: | 1600-0463 |
Popis: | Atorvastatin, a hydroxymethylglutaryl-CoA reductase inhibitor, and endothelin-1 (ET-1) receptor antagonist have been separately indicated to ameliorate disease progression in atherosclerosis. However, no study has evaluated the effect of their combination on atherosclerosis. The objective of the current study was to evaluate the direct in vivo effects of a combination regimen of atorvastatin and ET-1 receptor antagonist on male New Zealand white rabbit models of atherosclerosis (injury-induced). Thirty-two atherosclerotic rabbits were divided into four experimental groups: (a) injury group - fed high-fat diet; (b) ET-1 receptor antagonist preventive group - fed high-fat diet, but with intragastric administration of the ET-1 receptor antagonist, darusentan; (c) combined preventive group - fed high-fat diet, but with intragastric administration of both darusentan and atorvastatin; and (d) treatment group - fed high-fat diet for the first 8 weeks, followed by normal diet and intragastric administration of both darusentan and atorvastatin up to 16 weeks. A further eight non-atherosclerotic rabbits were fed normal diet and classified as the control group. At the end of 8 and 16 weeks, compared with the injury group, the combined preventive group had significant reduction in both the concentration of serum lipids and inflammatory factors and atherosclerosis formation, indicative of a multifaceted anti-atherosclerotic impact. The relative area of atherosclerotic lesions in the injury group (30.84%) was significantly higher than the control group (4.62%; p < 0.05). The combined preventive group showed a significantly robust effect on lowering serum lipid, inflammatory cytokines, and maintained homeostatic balance of free radicals, and important downstream effectors like ET-1 and matrixmetalloproteinase-9. Our data show that atorvastatin and ET-1 receptor antagonist co-administration may decrease lipid levels, stabilize plaques and relieve vascular inflammation. By reducing the plaque burden, this regimen may minimize the risk of atherosclerotic plaque rupture or arterial occlusion. |
Databáze: | OpenAIRE |
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