Τίτλος:
Antiatherosclerotic properties of EP2302, A novel squalene synthase inhibitor, in the cholesterol-fed rabbit
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2008 by Lippincott Williams & Wilkins.
Συγγραφείς:
Tavridou, A.
Kaklamanis, L.
Papalois, A.
Kourounakis, A.P.
Rekka, E.A.
Kourounakis, P.N.
Charalambous, A.
Manolopoulos, V.G.
Περιοδικό:
Journal of Cardiovascular Pharmacology
Λέξεις-κλειδιά:
alanine aminotransferase; aspartate aminotransferase; cholesterol; ep 2302; high density lipoprotein cholesterol; low density lipoprotein cholesterol; placebo; squalene synthase inhibitor; triacylglycerol; unclassified drug; antioxidant; biphenyl derivative; cholesterol; EP2302; lipid; morpholine derivative; squalene synthase, alanine aminotransferase blood level; animal experiment; animal model; animal tissue; article; ascending aorta; aspartate aminotransferase blood level; atherosclerosis; cholesterol blood level; cholesterol diet; controlled study; descending aorta; male; nonhuman; organ; priority journal; rabbit; toxicity; triacylglycerol blood level; animal; aorta; blood; coronary artery disease; diet; disease model; drug antagonism; drug effect; pathophysiology, Animals; Antioxidants; Aorta; Biphenyl Compounds; Cholesterol; Coronary Artery Disease; Diet; Disease Models, Animal; Farnesyl-Diphosphate Farnesyltransferase; Lipids; Morpholines; Rabbits
DOI:
10.1097/FJC.0b013e31817885fe
