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,Petri T Kovanen

doi:10.1194/jlr.m800058-jlr200

Abstract

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.

Highlights

The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves
The key observation of the present study was that serum noncholesterol sterols, including cholesterol precursors, plant sterols, and cholestanol, accumulate in stenotic aortic valve leaflets in a direct relation to their respective concentrations in serum
Dietary plant sterols or phytosterols are known for their serum LDL cholesterol-lowering effect, which results from their ability to compete with dietary and biliary cholesterol for intestinal absorption [38]

Summary

Introduction

The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves. 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.—Helske, S., T. Plant sterols or phytosterols compete with cholesterol for intestinal absorption, and food products containing plant sterols or their saturated derivatives, stanols, have been used alone or with statins to reduce serum cholesterol concentrations [24] The development of extremely early atherosclerotic disease, despite the presence of normal or only slightly elevated serum cholesterol levels but markedly increased phytosterol levels in these patients, suggests that plant sterols could be injurious to cardiovascular tissue [24]. Early presentation of supravalvular aortic stenosis has been described in a patient with phytosterolemia [28], suggesting that plant sterols could enter the supravalvular aortic tissue and perhaps even the aortic valve leaflets and participate in the pathogenesis of aortic valve disease in this rare metabolic condition

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