Pathogenesis of Vascular Disease

Long study of human post-mortem material and of the arterial disease in rabbits that follows cholesterol feeding has not yet resulted in an understanding of the pathogenesis of arteriosclerosis. Although the focal distribution of the lesions in man and the partition of their contained lipids suggest interactions of local and hemic factors, it has proven difficult to determine either the nature of these factors or to clarify their interrelationships. The report that follows describes an experimental procedure for the investigation of certain aspects of this subject. The technique utilized allows examination of the effects of altered blood lipids on the morphological sequences of experimentally produced inflammatory lesions of the aorta and coronary arteries of dogs. Anitschow' early spoke of a "combination theory" of the pathogenesis of arteriosclerosis and was able to demonstrate the deposit of lipids in the aortas of rabbits fed cholesterol and given epinephrine. The fact that it was quickly shown that the feeding of cholesterol alone resulted in fatty arterial lesions undoubtedly diverted attention from possible local factors involved in their establishment. More recently, Schlichter et al.'7 cauterized the aortas of cholesterol-fed dogs and reported fatty deposits at the site of the lesions in some instances. Kelly and Taylor and their associates'9'" have carried out similar experiments in rabbits and monkeys. The abdominal aorta was injured by freezing during the course of a high-fat, high cholesterol regimen and fatty transformations of the lesions so produced have been described and the subsequent processes of repair studied. Acute arterial lesions have also been produced in rabbits by sensitizing procedures during hypercholesterolemia." Acceleration of lipid deposit in the arterial lesions resulted.