Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve

Objective: To study in a rabbit model the expression of endothelial nitric oxide synthase (eNOS) in association with the development of calcification of the aortic valve, and to assess the effects of atorvastatin on eNOS expression, nitrite concentration, and aortic valve calcification. Methods: Rab...

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Bibliographic Details
Published in:Heart (British Cardiac Society) 2005-06, Vol.91 (6), p.806-810
Main Authors: Rajamannan, N M, Subramaniam, M, Stock, S R, Stone, N J, Springett, M, Ignatiev, K I, McConnell, J P, Singh, R J, Bonow, R O, Spelsberg, T C
Format: Article
Language:English
Subjects:
Animals
Anticholesteremic Agents - therapeutic use
aortic valve
Aortic Valve - enzymology
Atorvastatin Calcium
Basic Research
Biological and medical sciences
Blotting, Western
C-Reactive Protein - analysis
Calcification
Calcinosis - prevention & control
Cardiology. Vascular system
Cholesterol
Cholesterol - blood
computed tomography
endothelial nitric oxide synthase
Endothelium
eNOS
Heart Valve Diseases - blood
Heart Valve Diseases - enzymology
Heart Valve Diseases - prevention & control
Heptanoic Acids - therapeutic use
high sensitivity C reactive protein
HMG-CoA
hsCRP
hydroxymethyl glutaryl coenzyme A
Hypercholesterolemia - blood
Hypercholesterolemia - enzymology
Hypercholesterolemia - prevention & control
Laboratory animals
Male
Medical sciences
micro-CT
Nitric oxide
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type III
Nitrites - blood
Oxidative stress
Proteins
Pyrroles - therapeutic use
Rabbits
Signal transduction
statins
Studies
Tomography, X-Ray Computed - methods
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Summary:Objective: To study in a rabbit model the expression of endothelial nitric oxide synthase (eNOS) in association with the development of calcification of the aortic valve, and to assess the effects of atorvastatin on eNOS expression, nitrite concentration, and aortic valve calcification. Methods: Rabbits (n  =  48) were treated for three months: 16, forming a control group, were fed a normal diet; 16 were fed a 0.5% (wt/wt) high cholesterol diet; and 16 were fed a 0.5% (wt/wt) cholesterol diet plus atorvastatin (2.5 mg/kg/day). The aortic valves were examined with eNOS immunostains and western blotting. Cholesterol and high sensitivity C reactive protein (hsCRP) concentrations were determined by standard assays. Serum nitrite concentrations were measured with a nitric oxide analyser. eNOS was localised by electron microscopy and immunogold labelling. Calcification in the aortic valve was evaluated by micro-computed tomography (CT). Results: Cholesterol, hsCRP, and aortic valve calcification were increased in the cholesterol fed compared with control animals. Atorvastatin inhibited calcification in the aortic valve as assessed by micro-CT. eNOS protein concentrations were unchanged in the control and cholesterol groups but increased in the atorvastatin treated group. Serum nitrite concentrations were decreased in the hypercholesterolaemic animals and increased in the group treated with atorvastatin. Conclusion: These data provide evidence that chronic experimental hypercholesterolaemia produces bone mineralisation in the aortic valve, which is inhibited by atorvastatin.
ISSN:1355-6037
1468-201X
DOI:10.1136/hrt.2003.029785