title: Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves.
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.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland. satu.helske@wri.fi
authors.forename: Satu
authors.initials: S
authors.lastname: Helske
authors.forename: Tatu
authors.initials: T
authors.lastname: Miettinen
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.forename: Mikko
authors.initials: M
authors.lastname: Mäyränpää
authors.forename: Jyri
authors.initials: J
authors.lastname: Lommi
authors.forename: Heikki
authors.initials: H
authors.lastname: Turto
authors.forename: Kalervo
authors.initials: K
authors.lastname: Werkkala
authors.forename: Markku
authors.initials: M
authors.lastname: Kupari
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D000368:Aged; D001011:Aorta / Q000378:metabolism*; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood*; D003251:Constriction, Pathologic / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010840:Phytosterols / Q000097:blood*; D013185:Squalene / Q000097:blood
chemical_list: D010840:Phytosterols; D013185:Squalene; D002784:Cholesterol