The class
Chemically induced P-407 mouse model of hyperlipidemia indirectly raises CETP activity while directly inhibiting lipoprotein and hepatic lipase (J Cardiovasc Pharmacol 2004)
Original title: The P-407-induced murine model of dose-controlled hyperlipidemia and atherosclerosis: a review of findings to date
This review surveys findings on poloxamer 407 (P-407), a nonionic surfactant used to chemically induce dose-controlled hyperlipidemia and atherosclerosis in C57BL/6 mice without genetic modification, though a high-fat cholate-enriched diet potentiates the response. Across a panel of lipid-metabolism enzymes studied, P-407 directly inhibits the heparin-releasable fraction of lipoprotein lipase and hepatic lipase while indirectly increasing the biologic activity of both CETP and lecithin cholesterol acyltransferase, a pattern the authors suggest reflects a compensatory response to the model's rising cholesterol burden. The authors propose this chemical model as an alternative to genetic or diet-induced atherosclerosis models for evaluating newer antihyperlipidemic agents, including CETP inhibitors.
Original abstract
We are continuing to both elucidate underlying mechanisms and identify clinical applications for a chemically induced murine model of dose-controlled hyperlipidemia and atherosclerosis. This murine model neither utilizes genetically modified mice nor a high-fat, cholate-containing diet, although simultaneous ingestion of a high-fat, cholate-enriched diet potentiates the hyperlipidemic response and the number and size of aortic atherosclerotic lesions formed in C57BL/6 mice. The chemical agent used to induce hyperlipidemia is poloxamer 407 (P-407), a nonionic surface-active-agent. To date, we have investigated the effect of P-407 on the biologic activity of a variety of key enzymes involved with lipid metabolism and transport. These enzymes include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LPL), cholesterol 7alpha-hydoxylase (C7alphaH), sterol 27-hydroxylase (S27H), lecithin cholesterol acyltransferase (LCAT), cholesteryl-ester-transfer-protein (CETP), hepatic lipase (HL), and endothelial lipase (EL). P-407 directly inhibits the heparin-releasable fraction of LPL and HL and indirectly increases the biologic activity of CETP and LCAT. Long-term (> 4 months) administration of P-407 to C57BL/6 mice appears to have no effect on the biologic activity of S27H and HMG-CoA reductase, but decreases the activity of C7alphaH. This would suggest that hypertriglyceridemia and hypercholesterolemia result from inhibition of LPL and C7alphaH, respectively, while the biologic activity of CETP and LCAT are indirectly increased to compensate for the increased cholesterol burden. The above model has proven useful for predicting the therapeutic efficacy of existing and possibly newer statin drugs, as well as evaluating the potential of one statin drug (atorvastatin calcium) to cause the regression of P-407-induced atherosclerotic lesions in mice. The P-407-induced murine model of atherogenesis represents an alternative to the use of either genetically modified or diet-induced models and may also prove beneficial for the evaluation of newer classes of antihyperlipidemic agents such as antioxidants, CETP inhibitors, and liver X receptor (LXR) agonists.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.