No Association Between Plasma Levels of Plant Sterols and Atherosclerosis in Mice and Men

OBJECTIVE: Sitosterolemia is characterized by elevated plasma levels of plant sterols, hypercholesterolemia and premature coronary heart disease (CHD). CHD develops in some subjects with sitosterolemia, despite having normal plasma cholesterol levels, suggesting that high circulating levels of plant sterols may be atherogenic. We tested whether elevated plasma levels of plant sterols (sitosterol and campesterol) were associated with atherosclerosis in genetically modified mice and in middle-aged men and women. METHODS AND RESULTS: Wild-type and hypercholesterolemic female mice with >20-fold higher plasma levels of plant sterols because of inactivation of the ATP-binding cassette (ABC) half transporters G5 and G8 (G5G8-/-mice) were fed chow or Western diets for 7 months. No significant differences in aortic lesion area were found when the sitosterolemic mice were compared with littermate controls. To determine whether plasma levels of plant sterols were associated with coronary atherosclerosis in humans, the relationship between plasma plant sterols and coronary calcium (detected by electron beam computer tomography) was examined in 2542 subjects aged 30 to 67 years. Plasma levels of cholesterol, but not sitosterol or campesterol, were significantly higher in subjects with coronary calcium. CONCLUSIONS: The results of this study do not support an association between elevated plasma levels of plant sterols and atherosclerosis.