Poloxamer 407-induced atherogenesis in the C57BL/6 mouse

Area of Science:

• Cardiovascular Research
• Animal Models of Disease
• Lipid Metabolism

Background:

• Poloxamer 407 (P-407) is known to induce hyperlipidemia in rats.
• The C57BL/6 mouse strain is susceptible to hyperlipidemia-induced atherosclerotic plaque formation.

Purpose of the Study:

• To determine if chronic P-407 administration would produce atherogenic arterial lesions in C57BL/6 mice.
• To establish a novel animal model for studying diet- and chemically-induced atherosclerosis.

Main Methods:

• Four groups of C57BL/6 mice were treated for up to 300 days: saline control (C), P-407 injection (P), P-407 injection with cholic acid diet (PC), and high cholesterol/cholic acid diet (HF).
• Plasma lipid profiles, hepatic cholesterol, and aortic lesion areas were measured at multiple time points.

Main Results:

• P-407 administration significantly elevated plasma cholesterol in P and PC groups, reaching 600 mg/dl and 1000-1500 mg/dl, respectively.
• Atherogenic arterial lesions were observed in all treatment groups (P, PC, HF) by 90 days, with the largest lesions in the PC group.
• Lesion size progressively increased over 300 days, demonstrating sustained atherogenesis.

Conclusions:

• Chronic administration of Poloxamer 407 effectively induces hyperlipidemia and atherogenic arterial lesions in C57BL/6 mice.
• This study successfully established a chemical-agent-induced hyperlipidemia model for investigating atherogenesis.