Statin treatment of hypercholesterolemic-induced aortic valve sclerosis

Hamilton, Amanda M.; Boughner, Derek R.; Drangova, Maria; Rogers, Kem A.

doi:10.1016/j.carpath.2010.01.004

« Previous Next »Cardiovascular Pathology
Volume 20, Issue 2 , Pages 84-92, March 2011

Statin treatment of hypercholesterolemic-induced aortic valve sclerosis

Amanda M. Hamilton
- Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
- Imaging Research Laboratories, Robarts Research Institute, The University of Western Ontario, London, ON, Canada
Derek R. Boughner
- Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
- Department of Medicine, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
- Imaging Research Laboratories, Robarts Research Institute, The University of Western Ontario, London, ON, Canada
Maria Drangova
- Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
- Imaging Research Laboratories, Robarts Research Institute, The University of Western Ontario, London, ON, Canada
Kem A. Rogers
- Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
- Corresponding author. Department of Anatomy and Cell Biology, The University of Western Ontario, MSB M426, London, ON, Canada N6A 5C1. Tel.: +1 519 661 3995; fax: +1 519 661 3936.

Received 3 June 2009; received in revised form 8 December 2009; accepted 5 January 2010. published online 19 February 2010.

Abstract

Background

Aortic valve sclerosis (AVS) is a common inflammatory heart valve disease prevalent in the population over the age of 65 years. Several published clinical and animal studies have examined the ability of statin treatment to modify disease progression. Clinical trials yielded conflicting results, and animal studies examined the effects of statins prior to the onset of disease. Our study assessed the effect of dietary modification and/or statin treatment on established aortic valve disease in a rabbit model of AVS to examine the tissue response to therapy.

Methods

Aortic valve sclerosis was induced in male New Zealand White rabbits by dietary cholesterol supplementation. Rabbits were followed over 2.5 years, with the introduction of statins and/or dietary changes for the second half of the study. At end point, valve function was examined by magnetic resonance imaging. Excised aortic valve cusp tissue was surveyed for thickness, lipid accumulation, protein deposition, calcification, and cellular infiltration.

Results

By 15 months, cholesterol-fed valves exhibited thickening due to significant lipid content, macrophage infiltration, and osteopontin expression. By 30 months, the untreated disease had progressed to include elevated collagen deposition, lymphocyte invasion, and calcification. With treatment, however, the valve cusps exhibited significant pathological changes including diminished immune cell infiltration and osteopontin expression. Unfortunately, lipid was retained and calcification persisted in all treated valves.

Conclusions

In established AVS, the cellular response to statin therapy does not result in full regression of the sclerotic process.

Keywords: Statin treatment, Hypercholesterolemic-induced aortic valve sclerosis, Rabbit

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Financial support: This work was funded by the Heart and Stroke Foundation of Ontario [T6332]. M.D. is a Career Investigator of the Heart and Stroke Foundation of Ontario.

PII: S1054-8807(10)00020-7

doi:10.1016/j.carpath.2010.01.004

« Previous Next »Cardiovascular Pathology
Volume 20, Issue 2 , Pages 84-92, March 2011

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