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 rats and mice causes significant dose-dependent hypercholesterolemia and hypertriglyglyceridemia. The elevated triglycerides (TG) seem to result primarily from the compound's inhibition of lipoprotein lipase. P-407 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. These 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 be used as an agent for the study of hyperlipidemia-induced atherogenesis.
Palmer
W K
WK
School of Kinesiology, University of Illinois at Chicago, USA.
Emeson
E E
EE
Johnston
T P
TP
D000818:Animals; D001161:Arteriosclerosis / Q000139:chemically induced*; D002784:Cholesterol / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006949:Hyperlipidemias / Q000139:chemically induced*; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D011060:Poloxalene; D051381:Rats
D011060:Poloxalene; D002784:Cholesterol