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Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve
  1. N M Rajamannan1,
  2. M Subramaniam2,
  3. S R Stock5,
  4. N J Stone1,
  5. M Springett4,
  6. K I Ignatiev5,
  7. J P McConnell3,
  8. R J Singh3,
  9. R O Bonow1,
  10. T C Spelsberg2
  1. 1Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  2. 2Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA
  3. 3Department of Laboratory Medicine and Pathology, Mayo Clinic
  4. 4Electron Microscopy Core Facility, Mayo Clinic
  5. 5Institute for Bioengineering and Nanoscience in Advanced Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  1. Correspondence to:
    Dr Nalini M Rajamannan
    Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Tarry 12-703, Chicago, IL 60611, USA;


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.

  • CT, computed tomography
  • eNOS, endothelial nitric oxide synthase, HMG-CoA, hydroxymethyl glutaryl coenzyme A
  • hsCRP, high sensitivity C reactive protein
  • nitric oxide
  • statins
  • aortic valve
  • calcification
  • micro-CT

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