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 regression of atherosclerotic lesions in male apo E-deficient mice. Atherosclerosis was induced in fifteen mice by a "Western-type" diet containing 9% (w/w) fat 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, and the rest was divided into the control (n=6) and treated (n=7) groups. The 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 weeks (Regression phase). The mice developed severe hypercholesterolemia and advanced 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 of mice, the treated group had slightly smaller lesion size than the controls. During the induction phase, each mouse developed atherosclerotic lesions averaging 0.025 mm2 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 phase, the control group had a 40% increase in the lesion size, while this increase was only 28% in the treated animals. In conclusion, our previous findings along with a small decrease in the atherosclerotic lesion size observed in the treated group in the present study suggest that FCP-3PI treatment may slow the development of atherosclerotic lesions in apo E-deficient mice; however, a longer regression period may yield a greater benefit.
Moghadasian
M H
MH
Department of Pathology and Laboratory Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, Canada.
Godin
D V
DV
McManus
B M
BM
Frohlich
J J
JJ
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D010840:Phytosterols / Q000627:therapeutic use*; D014973:Xanthomatosis / Q000188:drug therapy
D001057:Apolipoproteins E; D010840:Phytosterols; D002784:Cholesterol