© 1997 American Heart Association, Inc.
Articles |
"Tall Oil"–Derived Phytosterols Reduce Atherosclerosis in ApoE-Deficient Mice
the Healthy Heart Program and Cardiovascular Research Laboratory, St. Paul's Hospital, and the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada. E-mail jifr@unixg.ubc.ca.
Correspondence to Jiri J. Frohlich, Department of Pathology and Laboratory Medicine, University of British Columbia, #180-1081 Burrard St, Vancouver, BC, Canada V6Z 1Y6.
We investigated the effects of a "tall oil"–derived phytosterol mixture (TODPM) on the formation of atherosclerotic lesions in apoE-deficient mice. TODPM was added at 2% (wt/wt) to the chow of nine mice; the control group had six animals. The diet of all animals contained 9% (wt/wt) fat and 0.15% (wt/wt) cholesterol. After 4 weeks, plasma total cholesterol levels were significantly reduced in the TODPM-treated mice (26.6 versus 42.0 mmol/L, P<.0001). The mean body weight of the TODPM-supplemented group was significantly higher at week 5 and throughout the study (29.4 versus 27.7 g, P<.05). The experiment was terminated at 18 weeks. Histological examination showed mature atherosclerotic lesions composed of foam cells underlying the endothelium, a mosaic of extracellular glycosaminoglycans, numerous apparently proliferative smooth muscle cells, and foci of cholesterol clefts in the control animals. By contrast, the TODPM-treated mice showed only early lesions containing mainly superficial foam cells. As assessed by morphometry, the lesion area in the aortic sinuses of TODPM-treated animals was less than half that of control animals (P<.0001). This reduced lesion area was accompanied by a substantial reduction in all lesional components, reflecting a delay in progression of atheromatous changes. A strong positive correlation (r=.69, P<.01) was found between plasma total cholesterol levels and lesion area in the aortic sinuses. TODPM also prevented the occurrence of xanthomatosis. We conclude that supplementation of a cholesterol-enriched diet with TODPM significantly lowers plasma cholesterol and retards development of atherosclerosis in apoE-deficient mice, suggesting a therapeutic potential for the mixture of phytosterols studied.
Key Words: cholesterol • phytosterols • apolipoprotein E–deficient mice • atherosclerosis
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