FACTORS ALTERING CONCENTRATION OF BLOOD LIPIDS 467 



the intima was first treated with certain cross-linking agents, of which 

 lead acetate is one of the most efficacious. On the basis of these results, 

 the hypothesis is advanced that the primary cause of cholesterol deposition 

 and the subsequent pathologic involvement of the arteries may be a chemi- 

 cal process affecting the protein material in the lining of the arteries. 

 These are changed from cholesterophobic to cholesterophilic substances, 

 presumably due to a gradual cumulative action on the part of certain 

 protein cross-linking agents. 



Injury may cause the formation of atheromas. Thus, Schlichter, Katz, 

 and Meyer 723 obtained some evidence that atheromas developed in dogs 

 when cholesterol was given following cauterization of the aortas, in con- 

 tradistinction to the negative results in the control animals which had not 

 been cauterized prior to the oral or intraperitoneal administration of 

 cholesterol. Moreover, Duff 724 demonstrated that injury to the intima 

 precedes the deposition of cholesterol in the blood vessels. The primary 

 cause of the atheroma may not be a hypercholesterolemia or a disturbance 

 in cholesterol metabolism, but rather a chemical disturbance in the tissue 

 which favors the deposition of cholesterol in a particular area. This 

 disturbance may be exaggerated or increased by high plasma levels of 

 cholesterol, and thus act as a contributory cause of atherosclerosis, al- 

 though Duff 724 failed to find direct evidence of any such effect. 



Another suggestion as to the relationship of blood cholesterol to athero- 

 sclerosis, by Alvarez and Neuschlosz, 725 is that the sterol is present in the 

 blood in this disease in a less readily soluble form; it is thought that, 

 under such conditions, cholesterol will precipitate even if present at normal 

 levels. However, neither Medvei 726 nor Holden 727 was able to substantiate 

 this theory. 



The formation of atheromas is believed to be related to the physical 

 state of the atherogenic agents. Thus, the large particles of fatty materials 

 in the blood during hyperlipemia are removed by the reticuloendothelial 

 cells in the arterial intima, and are retained due to the barrier action of the 

 internal elastic membrane. Moreton 728 demonstrated that this action was 

 not confined to lipid particles in the blood, but also occurred when other 

 coarsely suspended foreign substances, such as methyl cellulose, pectin, 

 and polyvinyl alcohol, were present in this fluid. Cholesterol deposition 



723 J. G. Schlichter, L. N. Katz, and J. Meyer, Am. J. Med. Set., 218, 603-609 (1949). 



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



728 C. Alvarez and S. M. Neuschlosz, Klin. Wochschr., 10, 244-247 (1931). 



729 C. V. Medvei, Klin. Wochschr., 11, 414-416 (1932). 

 727 R. F. Holden, Jr., J. Clin. Invest., 16, 763-765 (1937). 



725 J. R. Moreton, Science, 107, 371-373 (1948). 



