Document Detail

Aortic eNOS expression and phosphorylation in Apo-E knockout mice: differing effects of rapamycin and simvastatin.
MedLine Citation:
PMID:  15300198     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The inhibition of nitric oxide (NO) by hypercholesterolemia may be mediated, in part, by interactions with caveolin-1 (Cav-1). Because of the facilitatory effects of statins on endothelial function and the adverse effects of rapamycin (RAPA) on plasma lipids, we compared the effects of simvastatin (SMV) and RAPA on endothelial NO synthase (eNOS) and Cav-1 protein expression and phosphorylation in the aortas of apolipoprotein E (Apo-E) knockout (-/-) mice. METHODS: Apo-E -/- mice (n = 38) fed a high-cholesterol diet were given SMV (100 mg/kg/day po), RAPA (3 mg/kg/day ip), or no treatment for 10 weeks. Blood was drawn for serum lipid analysis, and protein was extracted for Western immunoblotting. Selected aortic specimens from 2 animals in each group were examined by histology and immunohistochemistry. The data are expressed as the mean +/- SEM and compared by the Student t test and ANOVA. Significance was established as P < .05. RESULTS: Lipid levels at 10 weeks were similar in the 3 groups except for higher triglyceride levels in RAPA-treated animals. eNOS expression was highest in RAPA-treated mice, but the p-eNOS to eNOS protein expression ratio was significantly greater in the SMV treatment group compared to both RAPA and controls (P < .05). Both Cav-1 and p-Cav-1 expression was significantly lower in the SMV-treated animals (P < .05) compared to mice treated with RAPA. CONCLUSIONS: Although eNOS expression was greatest in the RAPA-treated mice, the expression of p-eNOS was similar in the RAPA- and SMV-treated animals. The increase in eNOS induced by RAPA and the inverse relationship between p-eNOS and Cav-1 protein expression observed with SMV treatment suggest different mechanisms for the regulation of aortic eNOS expression in Apo-E mice by these 2 agents.
Joseph J Naoum; Shu Zhang; Kenneth J Woodside; Wei Song; Qian Guo; Ligia M Belalcazar; Glenn C Hunter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Surgery     Volume:  136     ISSN:  0039-6060     ISO Abbreviation:  Surgery     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-09     Completed Date:  2004-08-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  323-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2004 Elsevier Inc.
Department of Surgery, University of Texas Medical Branch at Galveston, TX 77555, USA.
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MeSH Terms
Aorta / enzymology*
Apolipoproteins E / physiology*
Caveolin 1
Caveolins / analysis
Cholesterol / blood
Endothelial Cells / physiology
Mice, Knockout
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Simvastatin / pharmacology*
Sirolimus / pharmacology*
Reg. No./Substance:
0/Apolipoproteins E; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Caveolins; 53123-88-9/Sirolimus; 57-88-5/Cholesterol; 79902-63-9/Simvastatin; EC Oxide Synthase; EC Oxide Synthase Type II; EC Oxide Synthase Type III; EC protein, mouse

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