Modulation of Hepatic Transcriptome in the Poloxamer P-407 Hyperlipidemia Mouse Model

Drago Kuzman,1,* Klementina Fon Tacer,2 M. Černe,1 Tadeja Režen,2 Jure Ačimovič,2 Urška Čegovnik,3 Darko Kocjan,1 Uroš Urleb1 and Damjana Rozman2

1 Lek Pharmaceuticals d.d., Ljubljana, Slovenia
2 Centre for Functional Genomics and Bio-Chips, Faculty of Medicine, University of Ljubljana, Slovenia
3 University Clinic for Pulmonary and Allergic Diseases Golnik, Golnik, Slovenia
* Corresponding author: E-mail:

The poloxamer P-407 hyperlipidemia mouse is a genetically unaltered, nondiet-induced model of atherosclerosis which is useful in studying effects of lipid lowering drugs. While the model is relatively well described on the biochemical level, the knowledge regarding the global gene expression was lacking so far. As expected, the P-407 elevates plasma triglycerides and cholesterol. Using microarray analysis and RT-PCR we show for the first time that poloxamer triggers a concerted modulation of hepatic genes involved in multiple steps of atherogenesis, such as lipid metabolism, initiation of atherogenesis, lesion formation, and atheroma progression. 106 hepatic genes were upregulated and only 40 downregulated, suggesting that upregulation of atherogenic genes precedes the atheroma formation. Modulated expression of circadian genes has also been observed in this type of hyperlipidemia but further studies are needed to elucidate whether this effects the rhythm of animals.

Keywords: Poloxamer, hyperlipidemia, atherogenesis, circadian