Lack of regression of atherosclerotic lesions in phytosterol-treated apo E-deficient mice

We evaluated the effects of a phytosterol mixture (FCP-3PI) on the regressi on of atherosclerotic lesions in male apo E-deficient mice. Atherosclerosis was induced in fifteen mice by a "Western-type" diet containing 9% (w/w) f at and 0.15% (w/w) cholesterol over a period of 18 weeks (Induction phase). Then, two mice were used to evaluate the development of atherosclerosis, a nd the rest was divided into the control (n=6) and treated (n=7) groups. Th e control group was fed mouse chow (4.5% w/w fat) and the treated group fed the same chow supplemented with 2% (w/w) FCP-3PI for an additional 25 week s (Regression phase). The mice developed severe hypercholesterolemia and ad vanced atherosclerotic lesions over the induction phase. During the first 6 weeks of regression phase, plasma cholesterol concentrations decreased at a similar rate (35%) in both groups of control and phytosterol-treated mice . Although evidence of lesion regression was not observed in either group o f mice, the treated group had slightly smaller lesion size than the control s. During the induction phase, each mouse developed atherosclerotic lesions averaging 0.025 mm(2) per week. However, during the regression phase, this was decreased to approximately one fifth and one third in the treated and control groups, respectively. Thus, compared to the end of the induction ph ase, the control group had a 40% increase in the lesion size, while this in crease was only 28% in the treated animals. In conclusion, our previous fin dings along with a small decrease in the atherosclerotic lesion size observ ed in the treated group in the present study suggest that FCP-3PI treatment may slow the development of atherosclerotic lesions in apo E-deficient mic e; however, a longer regression period may yield a greater benefit.