870 
ANATOMY AND PATHOLOGY 
Table X. — 'H-thymidine labeling indices of swine aortic 
tissue culture cells grown in 20% autologous serum 
Group* 
Labeling Index (%) 
P values** 
StSs 
21.5 
StSs<StCs p < .001 
StCs 
30.7 
StSs<CtCs p < .001 
CtSs 
22.5 
CtSs<CtCs p < .001 
CtCs 
31.4 
* StSs = Tissue from stock diet fed swine grown in serum from 
stock diet-fed swine; StCs = Tissue from stock swine in serum from 
cholesterol swine; CtSs = Tissue from cholesterol swine in serum 
from stock swine; CtCs = Tissue from cholesterol swine in serum 
from cholesterol swine. 
** Chi square test. 
at any given time when the cells are grown in 
hypercholesterolemic serum than when grown 
in control serum. One of these experiments is il- 
lustrated in Table X. 
In studies from other laboratories of skin, 
liver, and a few other tissues, evidence has been 
presented suggesting that normal plasma con- 
tains a cell-type-specific substance that inhibits 
cell multiplication in the target cell. In a few 
situations in which rate of cell multiplication is 
increased (for example, after partial hepatec- 
tomy) the available evidence from both in vivo 
and in vitro studies suggests that the amount of 
the cell-type-specific inhibitory substance is re- 
duced in the blood and in the affected tissue. We 
have just begun experiments designed to deter- 
mine whether or not such a substance exists for 
arterial SMC but do not as yet have sufficient 
results to warrant conclusions. 
SUMMARY 
A series of studies of arterial wall metabo- 
lism in cholesterol-fed swine has been pre- 
sented. These show that there is increased met- 
abolic activity from the earliest days on diet. 
The most significant manifestation from the 
standpoint of atherogenesis appears to be the 
excessive number of arterial SMC synthesizing 
DNA and dividing. From an overall point of 
view, the goal of all of the studies that were 
presented is to find an acceptable means to con- 
trol or prevent the development of the clinical 
manifestation of atherosclerosis in man. It is at 
least within the realm of possibility that this 
goal might be achieved by learning how to con- 
trol and prevent the excessive proliferation of 
arterial SMC that occurs so commonly in mod- 
ern man. 
REFERENCES 
1. Thomas, W. A., Florentin, R. A., Nam, S. C, 
Kim, D. N., Jones, R. M., and Lee, K. T. Pre- 
proliferative phase of atherosclerosis in swine fed 
cholesterol. Arch. Pathol. 86:621-643, 1968. 
2. Florentin, R. A., and Nam, S. C. Dietary- 
induced atherosclerosis in miniature swine. I. Gross 
and light microscopy observation: Time of devel- 
opment and morphologic characteristics of lesions. 
Exp. Mol. Pathol. 8:263-301, 1968. 
3. Scott, R. F., Jarmolych, J., Fritz, K. E., Imai, 
H., Kim, D. N., and Morrison, E. S. Reactions of 
endothelial and smooth muscle cells in the athero- 
sclerotic lesion. In Atherosclerosis: Proceedings of 
the Second International Symposium (R. J. Jones, 
ed.). Springer- Verlag, New York, pp. 50-58, 1970. 
4. Florentin, R. A., Nam, S. C, Lee, K. T., Lee, 
K. J., and Thomas, W. A. Increased mitotic activ- 
ity in aorta of swine after three days of cholesterol 
feeding. Arch. Pathol. 88:463-469, 1969. 
5. Scott, R. F., Morrison, E. S., and Kroms, M. 
Aortic respiration and glycolysis in the pre-prolif- 
erative phase of diet-induced atherosclerosis in 
swine. J. Atheroscler. Res. 9 : 5-16, 1969. 
6. Morrison, E. S., Scott, R. F., Kroms, M., and 
Pastori, S. J. A method for isolating aortic mito- 
chondria exhibiting high respiratory control. 
Biochem. Med. 4:47-54, 1970. 
7. Skinner, F., Scott, R. F., and Morrison, E. 
(Personal communication). 
8. Whereat, A. F. Fatty acid synthesis in cell-free 
system from rabbit aorta. J. Lipid Res. 7:671-677, 
1966. 
9. Kim, D. N., Lee, K. T., and Thomas, W. A. 
Dietary induced atherosclerosis in miniature swine. 
IV. Metabolic studies: In vitro protein synthesis by 
aortic strips from swine fed atherogenic diets. Exp. 
Mol. Pathol. 8:263-301, 1968. 
10. Imai, H., and Thomas, W. A. Cerebral atheroscle- 
rosis in swine. Role of necrosis in progression of 
dietary induced lesions from proliferative to ather- 
omatous stage. Exp. Mol. Pathol. 8:330-357, 1968. 
11. Imai, H., Lee, K. J., Lee, S. K., O'Neal, R. M., 
and Thomas, W. A. Degeneration of arterial 
smooth muscle cells: Ultrastructural study of 
smooth muscle cell death in control and cholester- 
ol-fed swine. Virchows Arch. Abt. A. Path. Anat. 
350:183-204, 1970. 
12. Baserga, R. Biochemistry of the cell cycle. A re- 
view. Cell Tissue Kinet. 1:167-191, 1968. 
13. FujiOKA, M., Koga, M., and Lieberman, I. 
Metabolism of ribonucleic acid after partial hepa- 
tectomy. J. Biol. Chem. 238:3401, 1963. 
14. Lamerton, L. F. Cell population kinetics in rela- 
tion to homeostasis. In Homeostatic Regulators 
(G.E.W. Waterholme and J. Knight, eds.), 
Churchill, London, pp. 5-28, 1969. 
15. Pelc, S. R. Incorporation of labeled precursors of 
DNA in non-dividing cells. In Cell Proliferation 
