Transgenic animals that do not express functional SR-BI and ApoE develop
severe atherosclerosis, by age four weeks in transgenic mice. Moreover,
these animals exhibit progressive heart dysfunction by as early as age
four weeks, and die by age nine weeks. This animal model has now been
demonstrated to be useful as a screen for compounds which alleviate the
symptoms of atherosclerosis and heart disease. Animals (Apo E-/-
SR-BI+/-) were fed PROBUCOL beginning at the time of mating. Offspring
are weaned at three weeks and fed PROBUCOL. In contrast to animals (Apo
E-/- SR-BI-/-) not fed PROBUCOL, 50% of whom are dead at six weeks, all
animals (Apo E-/- SR-BI-/-) on PROBUCOL have a normal phenotype (MRI of
heart function, ECG, echocardiogram, histology) at six weeks. At seven to
eight months, there is evidence of atherosclerosis and some myocardial
infarction. This demonstrates that the compound has a preventative
action. Animals who are taken off of the PROBUCOL all die within ten to
twelve weeks. In another study, the majority of animals whose parents
were not fed PROBUCOL, but who received the PROBUCOL beginning at about
five weeks of age, survived for a few months, demonstrating that the
compound also has a therapeutic benefit.