THE POLOXAMER 407-INDUCED HYPERLIPIDEMIC ATHEROGENIC ANIMAL-MODEL

We are attempting to develop a chemically-induced murine model for the study of atherosclerosis. Injection of poloxamer-407 (P-407) into rat s and mice causes significant dose-dependent hypercholesterolemia and hypertriglyglyceridemia. The elevated triglycerides (TG) seem to resul t primarily from the compound's inhibition of lipoprotein lipase. P-40 7 also indirectly stimulates the activity of the rate limiting enzyme in cholesterol (CHOL) biosynthesis, HMG CoA reductase. In addition, P- 407 promotes changes in the concentration of hepatic CHOL content. The se date indicate that the hyper CHOL could be the result of increased CHOL synthesis, as well as a clearing of CHOL from the liver. Chronic injection into mice of P-407 for 145 d produced atherogenic lesions in the aortas of C57BL/6 mice. The response was equivalent to that seen in animals eating a high CHOL diet for 145 d. Cholic acid potentiated the P-407-induced atherogenesis. These data suggest that P-407 could b e used as an agent for the study of hyperlipidemia-induced atherogenes is.