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Journal of Lipid Research, Vol. 49, 1511-1518, July 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves

Satu Helske^1,*, Tatu Miettinen, Helena Gylling, Mikko Mäyränpää^*,**, Jyri Lommi, Heikki Turto, Kalervo Werkkala, Markku Kupari and Petri T. Kovanen^*

^* Wihuri Research Institute, Helsinki, Finland
Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland
Department of Clinical Nutrition, University of Kuopio, Kuopio University Hospital, Kuopio, Finland
^** Department of Forensic Medicine, Helsinki University Central Hospital, Helsinki, Finland
Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
Division of Cardiothoracic Surgery, Helsinki University Central Hospital, Helsinki, Finland

Wihuri Research Institute is maintained by the Jenny and Antti Wihuri Foundation. This work was supported by the Finnish Foundation for Cardiovascular Research, Helsinki, Finland (SH); and by The Finnish Medical Foundation (SH).

Published, JLR Papers in Press, April 8, 2008.

¹ To whom correspondence should be addressed. e-mail: satu.helske{at}wri.fi

The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves. Since LDL particles also contain plant sterols, we investigated whether plant sterols accumulate in aortic valve lesions. Serum samples were collected from 82 patients with severe AS and from 12 control subjects. Aortic valves were obtained from a subpopulation of 21 AS patients undergoing valve surgery and from 10 controls. Serum and valvular total cholesterol and noncholesterol sterols were measured by gas-liquid chromatography. Noncholesterol sterols, including both cholesterol precursors and sterols reflecting cholesterol absorption, were detected in serum samples and aortic valves. The higher the ratios to cholesterol of the cholesterol precursors and absorption markers in serum, the higher their ratios in the stenotic aortic valves (r = 0.74, P < 0.001 for lathosterol and r = 0.88, P < 0.001 for campesterol). The valvular ratio to cholesterol of lathosterol correlated negatively with the aortic valve area (r = –0.47, P = 0.045), suggesting attenuation of cholesterol synthesis with increasing severity of AS. The higher the absorption of cholesterol, the higher the plant sterol contents in stenotic aortic valves. These findings suggest that local accumulation of plant sterols and cholesterol precursors may participate in the pathobiology of aortic valve disease.

Supplementary key words aortic stenosis • noncholesterol sterols • phytosterols • absorption

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