400 VIII. CHOLESTEROL AND RELATED STEROLS 



The mammary gland is also capable of effecting cholesterol synthesis 

 from acetate, even when it is in the non-lactating state. ^^^ The evidence 

 of Popjak and Beeckmans'^**--^^ that cholesterol is not sjaithesized in the 

 blood stream, but that plasma cholesterol is derived from the liver, seems 

 quite convincing. It is well known that the liver is likewise the site of syn- 

 thesis of plasma phospholipids (see The Lipids, Vol. II, pages 393-394). 



The source of the cholesterol in the lipid accumulations which occur in 

 atheromatosis is of great importance clinically. It was postulated by 

 early workers^^^--^^ that the plasma lipids were deposited in the wall of the 

 aorta and of the arterial system in general. Experimental support for this 

 hypothesis was adduced by Biggs and Kritchevsky,286 who demonstrated 

 by in vivo tests that the atheromatous rabbit obtains the bulk of its choles- 

 terol from the plasma, i.e., that the cholesterol is exogenous. However, 

 Siperstein et al.^^'' reported that the rat aorta can synthesize cholesterol 

 from labeled acetate in vitro. Werthessen and co-workers-^^ likewise ob- 

 served an in vitro synthesis of cholesterol in perfused bo\ine aorta. Shoi'e, 

 Zilversmit, and Ackerman-^^-^^° reported that the major portion of plaque 

 phospholipids in experimental rabbit atheromatosis was synthesized by the 

 aorta rather than derived from the plasma. This is of great interest, in- 

 asmuch as it indicates that the development of cholesterol plaques in the 

 aorta may represent a local synthesis of cholesterol from acetate rather 

 than the deposition of preformed cholesterol. ^^° In a continuation of this 

 study, Zilversmit and co-workers"^° confirmed their original finding, and 

 also demonstrated that plasma phospholipids accounted for only one-tenth 

 or less of the total phospholipids present in the atheromatous thoracic 

 aorta of the rabbit. 



It is thus evident that cholesterol can be synthesized from acetate in a 

 wide variety of tissues in addition to the liver. However, although Har- 

 per, Neal, and Hlavacek^^i confirmed the fact that cholesterogenesis may 

 take place in a large number of tissues, they found that only the liver has 



283 G. Popjdk and M. L. Beeckmans, Biochem. J., 44, xxxvii (1949). 



284 G. L. Duff, Arch. Pathol., 20, 81-123, 259-304 (1935). 



285 E. V. Cowdry, Arteriosclerosis. A Survey of the Problem, MacMillan, New York, 

 1933, pp. 254 ff. 



286 M. W. Biggs and D. Kritchevsky, Circulation, 4, 34-43 (1951). 



287 M. D. Siperstein, I. L. Chaikoff, and S. S. Chernick, Science, 113, 747-749 (1951). 



288 N. T. Werthessen, L. J. Milch, R. F. Redmond, L. L. Smith, and E. C. Smith, 

 Am. J. Physiol, 178, 23-29 (1954). 



289 M. L. Shore, D. B. Zilversmit, and R. F. Ackerman, Am. J. Physiol, 181, 527-531 

 (1955). 



29» D. B. Zilversmit, M. L. Shore, and R. F. Ackerman, Circulation, 9, 581-585 (1954). 

 2" P. V. Harper, Jr., W. B. Neal, Jr., and G. R. Hlavacek, Metabolism, 2, 69-80 

 (1953). 



