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Increased superoxide anion production is associated with early atherosclerosis and cardiovascular dysfunctions in a rabbit model

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Abstract

Objective

Hypercholesterolemia (HC) has been associated with impairment of vascular and myocardial functions. As HC could generate an alteration in the oxidative status, we studied the effects of a 1-month cholesterol diet on cardiovascular oxidative stress.

Methods and Results

New Zealand rabbits received cholesterol (1%) or normal chow for 1 month. At 30 days, superoxide anion levels, assessed by ESR spectroscopy, NAD(P)H oxidase (NOX) activity, and dihydroethidium (DHE) staining of aortas were higher in the cholesterol-fed (CF) group compared with control (respectively, 4.0 ± 0.6 Arbitrary Units/mg (AU/mg) vs. 2.6 ± 0.3, p < 0.05; 4231 ± 433 vs. 2931 ± 373 AU/mg, p < 0.05; 21.4 ± 1.2 vs. 12.9 ± 1.7% fluorescence/mm2, p < 0.001). NOX gp91phox and p67phox expression in the aortas were higher in the CF group vs. control (1.5 ± 0.2 vs. 0.5 ± 0.2, p < 0.001; 0.9 ± 0.2 vs. 0.3 ± 0.2, p < 0.05). The endothelium-dependent relaxation evaluated on the iliac arteries was higher in control than in the CF group (64.8 ± 10.1 vs. 13.1 ± 3.70%, p < 0.001). The cardiac diastolic pressure estimated on isolated hearts was higher in the CF group than in control (21.1 ± 4.1 vs. 10.3 ± 1.4 mmHg, p < 0.05) after 60 min of ischemia.

Conclusions

Hypercholesterolemia induced increased levels of superoxide in the aortas and a higher expression of NOX subunits, associated with altered vasorelaxation. The increased diastolic pressure observed in hearts, consistent with a post-ischemic contractile dysfunction might be mediated by the production of superoxide.

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Acknowledgments

The authors gratefully acknowledge l’Association de Cardiologie de Bourgogne, le Commissariat à l’Energie Atomique, Philip Bastable (editorial assistance), Professor Philip Gambert (Biochemistry Department, University Hospital of Dijon) and Franck Ménétrier (Histology Department, Faculty of medicine of Dijon) for technical assistance.

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Authors and Affiliations

  1. Laboratory of Cardiovascular and Experimental Physiopathology and Pharmacology, Faculty of Medicine, IFR n°100, University of Burgundy, 7, Boulevard Jeanne d’Arc, 21079, Dijon Cedex, BP 87900, France

    Bertrand Collin, David Busseuil, Marianne Zeller, Caroline Perrin, Olivier Barthez, Catherine Vergely, Marc Bardou, Monique Dumas & Luc Rochette

  2. IFR n°100, INSERM U498, CHU Bocage, 21034, Dijon, France

    Laurence Duvillard

  3. Cardiology Department, CHU Bocage, 21034, Dijon, France

    Yves Cottin

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  1. Bertrand Collin
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  2. David Busseuil
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  3. Marianne Zeller
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Correspondence to Bertrand Collin.

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Collin, B., Busseuil, D., Zeller, M. et al. Increased superoxide anion production is associated with early atherosclerosis and cardiovascular dysfunctions in a rabbit model. Mol Cell Biochem 294, 225–235 (2007). https://doi.org/10.1007/s11010-006-9263-y

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  • DOI: https://doi.org/10.1007/s11010-006-9263-y

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