TALL OIL-DERIVED PHYTOSTEROLS REDUCE ATHEROSCLEROSIS IN APOE-DEFICIENT MICE

We investigated the effects of a ''tall oil''-derived phytosterol mixt ure (TODPM) on the formation of atherosclerotic lesions in apoE-defici ent 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% (w t/wt) fat and 0.15% (wt/wt) cholesterol. After 4 weeks, plasma total c holesterol 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 a t 18 weeks. Histological examination showed mature atherosclerotic les ions composed of foam cells underlying the endothelium, a mosaic of ex tracellular glycosaminoglycans, numerous apparently proliferative smoo th muscle cells, and foci of cholesterol clefts in the control animals . By contrast, the TODPM-treated mice showed only early lesions contai ning mainly superficial foam cells. As assessed by morphometry, the le sion 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, ref lecting a delay in progression of atheromatous changes. A strong posit ive correlation (r=.69, P<.01) was found between plasma total choleste rol 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 cho lesterol and retards development of atherosclerosis in apoE-deficient mice, suggesting a therapeutic potential for the mixture of phytostero ls studied.