POLOXAMER 407-INDUCED ATHEROGENESIS IN THE C57BL 6 MOUSE/

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.