Submitted on February 1, 2008
Revised on April 4, 2008
Accepted on April 4, 2008
Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves
Satu Helske, Tatu Miettinen, Helena Gylling, Mikko Mäyränpää, Jyri Lommi, Heikki Turto, Kalervo Werkkala, Markku Kupari, and Petri Kovanen
Wihuri Research Institute, Wihuri Research Institute, Helsinki 00140
Corresponding Author: satu.helske{at}wri.fi
Background- The pathogenesis of aortic valve stenosis (AS) is characterized by accumulation of LDL-derived cholesterol in the diseased valves. Since LDL particles also contain plant sterols, we investigated whether plant sterols accumulate in aortic valves lesions. Methods- 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 non-cholesterol sterols were measured by gas-liquid chromatography (GLC). Results- Non-cholesterol sterols, including both cholesterol precursors and sterols reflecting cholesterol absorption were detected in serum samples and aortic valves. The higher were the ratios to cholesterol of the cholesterol precursors and absorption markers in serum, the higher were their ratios also in the stenotic aortic valves (e.g. 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. Conclusions- The higher was the absorption of cholesterol, the higher were also 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.
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