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The poloxamer 407-induced hyperlipidemic atherogenic animal model
W K Palmer1, E E Emeson, T P Johnston
1School of Kinesiology, University of Illinois at Chicago, USA.
Medicine and Science in Sports and Exercise
|December 31, 1997
Summary
Poloxamer-407 (P-407) induces hyperlipidemia in mice, leading to dose-dependent increases in cholesterol and triglycerides. Chronic P-407 administration results in atherogenic lesions, suggesting its utility in studying atherosclerosis.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Animal Models
Background:
- Atherosclerosis is a significant health concern.
- Developing reliable animal models is crucial for studying atherosclerosis.
- Hyperlipidemia is a key risk factor for atherosclerosis.
Purpose of the Study:
- To develop a chemically-induced murine model for atherosclerosis research.
- To investigate the effects of poloxamer-407 (P-407) on lipid metabolism and atherogenesis in mice.
Main Methods:
- Mice and rats were injected with varying doses of poloxamer-407 (P-407).
- Lipid profiles (cholesterol, triglycerides) were analyzed.
- Hepatic cholesterol metabolism and enzyme activity (HMG CoA reductase, lipoprotein lipase) were assessed.
- Chronic P-407 administration (145 days) was performed in C57BL/6 mice.
- Atherogenic lesions in aortas were evaluated.
- The effect of cholic acid co-administration was studied.
Main Results:
- P-407 induced dose-dependent hypercholesterolemia and hypertriglyceridemia.
- Elevated triglycerides were linked to lipoprotein lipase inhibition.
- P-407 stimulated cholesterol biosynthesis via HMG CoA reductase.
- Hepatic cholesterol content was altered, suggesting increased synthesis and clearance.
- Chronic P-407 treatment in mice led to atherogenic aortic lesions.
- Lesion severity was comparable to high cholesterol diet models.
- Cholic acid potentiated P-407-induced atherogenesis.
Conclusions:
- Poloxamer-407 (P-407) effectively induces hyperlipidemia in rodents.
- P-407 administration leads to the development of atherogenic lesions in mice.
- This P-407-induced model is suitable for studying hyperlipidemia-induced atherosclerosis.
