THOMAS B. CLARKSON 
17 
cholesterol.^"'^^ Diet exacerbated lesions in 
squirrel monkeys are somewhat less extensive 
and complex than diet-induced lesions of rhesus 
monkeys. Most commonly, the aortas from cho- 
lesterol-fed squirrel monkeys will have exten- 
sive fatty streaking covering almost the entire 
intimal surface with numerous small plaques 
about 2 or 3 mm in diameter affecting about 
40% of the thoracic aorta and about 20% of the 
abdominal aorta. Coronary artery lesions are 
small and infrequent in the proximal main 
branches but common and extensive in the 
small intramyocardial branches. 
Among squirrel monkeys fed cholesterol, cer- 
tain individuals (hyperresponders) develop se- 
vere hypercholesterolemia while others (hypo- 
responders) fed the same diet maintained 
plasma cholesterol concentrations near that of 
controls. The result of recent experiments sug- 
gests that these differences are genetically 
determined.^- Hypo- and hyperresponder squir- 
rel monkeys, by selective breeding, have been 
used to develop strains of squirrel monkeys 
with these metabolic characteristics. Hypo- 
responder squirrel monkeys when fed choles- 
terol-containing diets even for a long period have 
only minimal arterial lesions. In contrast, how- 
ever, the atherosclerosis of hyperresponder 
monkeys is markedly exacerbated. The lesions 
seen in hyperresponder monkeys are essentially 
the same as those that we have previously 
reported^" except that they are more extensive 
and severe and lesions frequently associated 
with hyperlipidemia are seen in other organs. 
About half of hyperresponder monkeys have cu- 
taneous xanthomatosis and an occasional ani- 
mal will have xanthelasma. When xanthomto- 
sis occurs it is most often present on the planter 
or palmer surfaces. 
Using formula diets and sterol balance tech- 
niques cholesterol absorption, synthesis, excre- 
tion, and turnover have been compared in hypo- 
and hyperresponding monkeys. Cholesterol 
absorption, synthesis and excretion of neutral 
steroid were similar for hypo-and hyper- 
responders; however, hyporesponders were 
found to have increased bile acid excretion short- 
ly after cholesterol feeding was begun, which 
was present among hyperresponders to a much 
lesser degree. These experiments have suggested 
that the mechanism of control of plasma choles- 
terol concentrations in cholesterol-fed squirrel 
monkeys is related to the rate of conversion of 
cholesterol to bile acids. -'' 
Squirrel monkeys have also been found to be 
useful animal models for studies on the contri- 
bution of the intestinal wall to the biosynthetic 
origin of serum cholesteroP^ and for studies on 
the effect of dietary cholesterol on the relative 
rates of synthesis in various tissues.^^ Addi- 
tionally, the usefulness of these animals has 
been shown for studies on the effect of dietary 
fat on whole body sterol metabolism. 
Atherosclerotic aortas have been studied met- 
abolically by St. Clair and co-workers. ^'^ The 
changes in lipid metabolism of the diseased aor- 
tas resemble those reported as occurring in 
other species. Among the fatty acids esterified 
to cholesterol the amount of cholesteryl oleoate 
increased the most. Additionally, synthesized 
fatty acids incorporated into cholesteryl esters 
were increased approximately six-fold in the 
atherosclerotic aortas compared to controls. 
Squirrel monkeys have been used to study the 
effect of carbon monoxide on the extent and se- 
verity of atherosclerosis.^^ In that seven month 
study the atherosclerosis induced in the coro- 
nary arteries was aggravated by carbon monox- 
ide but aortic atherosclerosis was not. Among 
the monkeys exposed to carbon monoxide there 
was more intimal lipid in each coronary artery 
atherosclerotic plaque rather than more coro- 
nary arteries being affected with atheoscle- 
rosis. 
Lehner and co-workers^" reported on the ef- 
fect of insulin deficiency, hypothyroidism, and 
hypertension on diet exacerbated atheroscle- 
rosis of squirrel monkeys. Insulin-deficient, hy- 
pothyroid, and hypertensive monkeys were 
found to have more extensive coronary artery 
and aortic atherosclerosis than did controls. 
Atherosclerosis was especially severe in the in- 
sulin-deficient monkeys. This study suggested 
that the squirrel monkey may be a good animal 
in which to study the mechanisms by which 
these disorders affect atherosclerosis. 
CEBUS MONKEYS (Cebus albifrons) 
Cebus albifrons monkeys are among the spe- 
cies in which the earliest studies were done on 
