Chronic Models in Higher Species

In contrast to rodents, animals such as rabbits, who naturally express high CETP activity, are spontaneously susceptible to diet-induced atherosclerosis. Rabbit models of atherosclerosis have been used to define the long-term quantitative efficacy of experimental drug products on lesion progression under more chronic conditions. These models typically require dosing up to 6 months or longer. Transgenic rabbit models have also confirmed the contributions that various gene products make to disease progression in rabbits, including apolipoproteins (apo(a), apoA-I, apoB, apoE), hepatic lipase (HL), LCAT, LpL, and 15-LO.33 Primate models of atherosclerosis have also been employed to define the long-term efficacy of experimental drugs for up to 1 year of dosing.

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