Wk. Palmer et al., THE POLOXAMER 407-INDUCED HYPERLIPIDEMIC ATHEROGENIC ANIMAL-MODEL, Medicine and science in sports and exercise, 29(11), 1997, pp. 1416-1421
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.