THOMAS B. CLARKSON 
15 
able tendency of rhesus monkey to develop 
cutaneous and tendonous xanthomatosis.^^ 
Xanthelasma has been noted in two hypercholes- 
terolemic animals in our colony. 
Pickering and his group were the first to 
study the effect of infant formulas on serum 
lipid levels of rhesus monkeys.^ ^ Formulas con- 
taining either milk fat or vegetable fat were fed 
to infant rhesus monkeys for 350 days. The 
monkeys fed the formula with milk fat had sig- 
nificantly higher serum cholesterol levels 
(275-404 mg%) than those fed the vegetable 
fat formula (133-188 mg% ) . After 350 days of 
feeding, autopsies were done on the animals. No 
differences could be found in the frequency of 
arterial lesions in the two groups of animals. 
Greenberg and Gonzalez^^ extended the stud- 
ies of Pickering and co-workers. They fed in- 
fant rhesus monkeys liquid diets that contained 
either monkey milk, human milk, or one of two 
prepared formulas that contained either bovine 
butterfat or a mixed fat with a 1 :1 ratio of poly- 
unsaturated to saturated fatty acids. The 
monkeys were fed the diets for 8-12 months. 
Arterial lesions were essentially similar in all 
groups. The monkeys fed human milk had the 
highest incidence of vascular lesions but the au- 
thors concluded that this was probably "a coin- 
cidental finding." 
Because of the general suitability of diet- 
induced atherosclerotic lesions of rhesus mon- 
keys, these animals are being used increasingly 
for studies on lesion regression. Armstrong and 
his co-workers^° have reported on an extensive 
study of lesion regression in rhesus monkeys. In 
their experiment, forty adult male rhesus mon- 
keys were first fed an atherogenic diet for 17 
months and the base line extent of atheroscle- 
rosis was determined in a representative sample 
of ten monkeys. Most had fatty streaks and un- 
complicated plaques. The remaining animals 
were divided into two groups and fed diets con- 
taining no cholesterol : one low in fat, the other 
high in unsaturated fat. After 40 months of 
being fed these diets the atherosclerosis was 
again accessed. Stenosis of the lumens of coro- 
nary arteries was markedly decreased, as was 
free and ester cholesterol in the arteries, but a 
fibrous plaque of considerable size remained. 
More recently Tucker and his co-workers^^ 
have studied the regression of diet-induced aor- 
tic fatty streaks in rhesus monkeys. The "re- 
gression group" in this experiment was fed a 
cholerterol-containing diet for two months and 
then normal monkey chow for four months. In 
all three of the regressed animals studied the 
intimal smooth muscle cells contained much less 
lipid than controls. Most of the smooth muscle 
cells contained no lipid at all and only a very 
few contained any significant quantities of 
lipid. In contrast, however, the extracellular 
lipid appeared more abundant and there was 
more collagen in the "regressed lesions" than 
controls. 
CYNOMOLGUS MACAQUE (Macaca fascicularis) 
Cynomolgus or crab-eating macaques were 
previously designated as Macaca irus and more 
recently as Macaca fascicularis. Although only 
two groups have reported using these monkeys 
in atherosclerosis research it seems likely that 
they will have considerable potential as animal 
models. Malmros and his co-workers were the 
first to report on the use of these animals in 
1965.'*2 They investigated the effect of a hydro- 
genated coconut oil diet, a corn oil diet, and a 
diet containing hydrogenated coconut oil and 
5 % cholesterol on the serum cholesterol concen- 
tration of animals of this species. The fats alone 
appeared to have affected the serum cholesterol 
concentration similarly with the levels being 
100-150 mg%. The addition of 5% cholesterol 
to the hydrogenated coconut fat diet resulted in 
an initial increase to about 450 mg% with a 
gradual plateau to about 300 mg%. On the basis 
of their observations one would be tempted to 
conclude that macaques of this species are con- 
siderably more resistant to the effects of dietary 
cholesterol than rhesus monkeys. This appears, 
however, not to be the case. We have recently 
initiated experiments in our laboratories in 
which we are feeding a semisynthetic diet con- 
taining 0.5% cholesterol to Macaca fascicularis 
monkeys. In our experience a hypercholes- 
terolemia of 1000 mg% occurred in two months. 
The striking differences in the hypercholes- 
terolemic response of various species of mon- 
keys to diets that differ from laboratory to labo- 
ratory is a little recognized but most important 
phenomenon. 
