ANIMAL MODELS OF ATHEROSCLEROSIS 
Thomas B. Clarkson* 
Recent research on the suitability of animal models 
for research on atherosclerosis has involved numerous 
studies on nonhuman primates. This interest has devel- 
oped because of the belief that data obtained from 
these animals may be more directly related to under- 
standing atherosclerosis of human beings than that ob- 
tained from lower animals. Diet-induced atherosclerosis 
has been studied in certain of the apes and Old World 
monkeys, particularly chimpanzees (Pan troglodytes), 
baboons (Papio species), rhesus monkeys (Macaca 
mulatta), and Cynomolgus macaques (Macaca 
fascicularis). Among the New World monkey species 
diet-induced atherosclerosis has been most studied in 
squirrel monkeys (Saimiri sciureus) and cebus mon- 
keys (Cebus albifrons). These nonhuman primates vary 
considerably in the characteristics of their lipid metabo- 
lism and the extent, severity, and morphology of their 
atherosclerosis. From the available information the in- 
vestigator can now choose the species best suited for 
the facet of atherosclerosis that is under study. 
INTRODUCTION 
The availability of animal models for re- 
search on atherosclerosis is particularly impor- 
tant because of the limitation of the kinds of 
experiments that can be done using human sub- 
jects. Until recently progress in research on 
atherosclerosis was hindered by the lack of sat- 
isfactory animal models. Practically all experi- 
ments were done on chickens or rabbits, and in 
some instances the findings had dubious rele- 
vance to the human disease. Since the late 
1950's there has been a considerable national ef- 
fort directed toward the characterization of 
more appropriate animal models. Of particular 
importance have been studies dealing with the 
characteristics of naturally-occurring and in- 
duced atherosclerosis of nonhuman primates. 
This recent emphasis on nonhuman primates as 
animal models of atherosclerosis developed be- 
cause of the widely held belief that data derived 
from experiments on these animals may be 
* Arteriosclerosis Research Center, Bowman Gray School of Medi- 
cine of Wake Forest University, Winston-Salem, North Carolina 
more directly applicable to man than those ob- 
tained from lower animals. The purpose of this 
communication is to summarize some of the ob- 
servations on lipid metabolism and atheroscle- 
rosis of the nonhuman primate species that are 
currently of interest in atherosclerosis research. 
CHIMPANZEE (Pan troglodytes) 
Several studies have been done on the 
natural occurrence of atheroclerosis in 
chimpanzees.^ ^■'^ One of the most extensive of 
these is that by Strong et al.* In that study the 
aortas of 14 chimpanzees, 21 to 90 months old, 
were examined for the presence of sudanophilic 
intimal lesions. Fatty streaks were found in 11 
of the 14 aortas; however, no fibrous plaques, 
complicated, or calcified lesions were present. 
Vastesaeger and Delcourt^ reported that two 
chimpanzees necropsied at the Antwerp Zoo 
had lesions in the aorta and coronary artery le- 
sions containing foam cells and cholesterol crys- 
tals. 
The plasma cholesterol concentration of 
chimpanzees is comparatively low among ani- 
mals consuming diets natural to the species. 
Mann^ fed young chimpanzees for several years 
purified diets with a small amount of added 
fruit. With the addition of a small daily intake 
of 200 mg per day of cholesterol, a hypercholes- 
terolemia of 400 to 500 mg% resulted. The 
addition of cysteine to the diet, which already 
contained 20% casein, increased the animals' 
tolerance for dietary cholesterol. Without addod 
cysteine, Mann states that chimpanzees are 
about five times more sensitive to dietary choles- 
terol than are rabbits. 
Andrus, Portman and Riopelle^ studied 14 
chimpanzees maintained for one year on semi- 
purified high fat diets (some of which also con- 
tained 1 mg of cholesterol per calorie). With 
few exceptions their animals were sexually ma- 
ll 
