Abstract 23244: Lipid Profiling of Dyslipidemic Animal Models
In an attempt to understand the predictivity of animal models for study of dyslipidemia, we analyzed plasma lipid and metabolic profiles across 5 mouse strains, 6 other non-primate species and 5 primate species including dyslipidemic humans to 2-week simvastatin treatment. Plasma fatty acid composition, lipoproteins and lipid classes were examined through lipomics and other metabolic parameters. When examining the responsiveness to simvastatin of circulating cholesterol ester (CE), triglycerides (TG) and phosphatidylcholine (PC), we found significant species differences in the responsiveness of these lipid classes. In general, all non-rodent species decreased CE excepting marmosets, TG decreases were observed in humans, African green and cynomolgus monkeys, but not in rhesus macaques, marmosets or rabbits. Interestingly, rabbits had an exaggerated decrease of CE and a nonsignificant increase in TG. All species had modest or non-significant decrease of PC. When examining the rodent strains, little response to simvastatin was observed with the exception of the ZDF rat wherein there was no response to CE but a very robust decrease of both TG and PC. When absolute levels of cholesterol and other lipids are measured, most historical literature models for atherosclerosis and dyslipidemia (mouse and rabbit) fall out of the range of humans; primates, pig, dog, and hamster more closely resemble humans. In aggregate, across all measures, non-human primates are the model that most reflects humans as accurate models for target validation and lead identification.
- © 2010 by American Heart Association, Inc.