Poloxamer 407 (P-407) induces hyperlipidemia in the rat. It was the pu
rpose of this investigation to determine if chronic P-407 administrati
on would produce atherogenic arterial lesions in the C57BL/6 mouse, a
strain reported to be susceptible to hyperlipidemia-induced atheroscle
rotic plaque formation. One injection (i.p.) of P-407 (0.5g/kg) produc
ed hypercholesterolemia in the mouse that peaked at 24 h and returned
to control levels by 96 h following treatment. Four groups of mice wer
e maintained: (1) saline injected (C); (2) P-407-injected (0.5g/kg eve
ry 3rd day) (P); (3) P-407 injected plus cholic acid in the diet (PC);
and (4) mice fed a high cholesterol (CHOL) diet containing cholic aci
d (HF). Mice from each group were sacrificed following 90, 145, 200, o
r 300 days of treatment. Plasma lipid concentrations, hepatic CHOL con
centrations (145 and 300 day), and aortic atherogenic lesion areas wer
e measured. Plasma CHOL and triglyceride remained at control levels th
roughout the 300 days in the C group. CHOL of the HF animals plateaued
at approximately 225 mg/dl. P-407 produced CHOL concentrations of 600
mg/dl in P mice and 1000-1500 mg/dl in PC animals. There was no lesio
n formation in C mice. However, by 90 days lesions were present in the
three other groups. Size of the lesions progressed through day 300 wi
th the largest lesions (184.33 + 27.99 mu(2) x 10(-3)) being present i
n the PC mice. HF and P animals had lesions of 70.50 + 11.35 and 43.33
+ 7.88 mu(2) x 10(-3), respectively. This study provides an animal mo
del where atherogenesis has been produced with hyperlipidemia induced
using a chemical agent. (C) 1998 Elsevier Science Ireland Ltd.