Thirty-five
apo E-deficient mice fed a high-
cholesterol diet were included in the study. Control mice were killed at 20 (n=8) or 25 (n=7) weeks. Treated mice received 18
injections of either 40 mg/kg
apo A-I(Milano)/PC (n=15) or PC only (n=5) intravenously every other day from 20 weeks until death at 25 weeks. Aortic
atherosclerosis was identified with
Sudan IV staining.
Lipid and macrophage contents of the aortic sinus plaques were measured after
oil-red O and Mac-1 antibody staining, respectively, and quantified with computed morphometry. In control mice, from 20 to 25 weeks, aortic
atherosclerosis increased by 59% (11 +/- 1% versus 17 +/- 5% of the aortic surface, P=.002), and
lipid content increased by 45% (22 +/- 8% versus 32 +/- 6% of plaque area, P=.02) without a significant change in macrophage content (10.8 +/- 2% versus 13.2 +/- 6%). Compared with 20-week-old untreated control mice, PC only-treated mice at 25 weeks demonstrated a 32% increase in aortic
atherosclerosis (11 +/- 1% versus 15 +/- 4%, P=.01) and an increase in
lipid content (22 +/- 8% versus 47 +/- 3%, P<.0001) without a change in macrophage content (10.8 +/- 2% versus 11 +/- 2%). In comparison with 20-week-old untreated control mice, 25-week-old
apo A-I(Milano)/PC-treated mice demonstrated no increase in aortic
atherosclerosis (11 +/- 1% versus 10 +/- 4%, P=NS), a 40% reduction in
lipid content (22 +/- 8% versus 13 +/- 8%, P=.01), and a 46% reduction in macrophage content (10.8 +/- 2% versus 5.8 +/- 2.9%; P=.03). Serum
cholesterol levels were markedly elevated in all groups and did not change significantly with
apo A-I(Milano)/PC or PC only. In vitro,
apo A-I(Milano)/PC stimulated
cholesterol efflux from
cholesterol-loaded FU5AH
hepatoma cell lines in a dose-dependent manner, whereas PC only or PC-free
apo A-I(Miano) had no effect.
CONCLUSIONS: