Document Detail


Antiatherosclerotic properties of EP2302, a novel squalene synthase inhibitor, in the cholesterol-fed rabbit.
MedLine Citation:
PMID:  18520953     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
EP2302 is a novel nitric oxide donor compound that inhibits squalene synthase. We hypothesized that EP2302 can reduce atherosclerosis in the cholesterol-fed rabbit atherosclerosis model. Animals were fed a high-cholesterol (HC) diet for 4 weeks. Animals subsequently received drug or placebo for 4 (n = 15) or 12 weeks (n = 15) while on HC diet. A third group (n = 16) received drug or placebo for 4 weeks while on regular diet (regression group). No significant differences were observed in circulating lipids among any of the treatment groups at each time point during HC intake. The perimeter and area of the ascending aorta covered by lesions were significantly decreased in animals treated with 2 mg/kg EP2302 for 4 weeks (44% and 42% reduction, respectively). Moreover, a significant decrease in the perimeter of the ascending and descending aorta covered by lesions was observed in animals treated with 2 mg/kg EP2302 for 12 weeks (73% and 44% reduction, respectively) as well as in the regression group (61% and 65% reduction, respectively). Treatment with EP2302 did not cause any toxicity in animal vital organs. We have shown that EP2302 inhibits atherosclerosis in the cholesterol-fed rabbit and therefore may serve as a candidate drug to be tested in humans for atherosclerosis-related disorders.
Authors:
Anna Tavridou; Loukas Kaklamanis; Apostolos Papalois; Angeliki P Kourounakis; Eleni A Rekka; Panos N Kourounakis; Avgui Charalambous; Vangelis G Manolopoulos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  51     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-07-08     Completed Date:  2008-10-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  573-80     Citation Subset:  IM    
Affiliation:
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / adverse effects,  pharmacology*
Aorta / drug effects*,  physiopathology
Biphenyl Compounds / adverse effects,  pharmacology*
Cholesterol / adverse effects*
Coronary Artery Disease / prevention & control*
Diet
Disease Models, Animal
Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
Lipids / blood
Morpholines / adverse effects,  pharmacology*
Rabbits
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Biphenyl Compounds; 0/EP2302; 0/Lipids; 0/Morpholines; 57-88-5/Cholesterol; EC 2.5.1.21/Farnesyl-Diphosphate Farnesyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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