Experimental induction of athero-arteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. I. Effect of repeated injections of horse serum in rabbits fed a dietary cholesterol supplement.
In rabbits that received a dietary supplement of cholesterol, 0.5% by weight, and concommittant injections of horse serum (group III) over a period of 80 days, coronary arterial lesions developed that in the main were different in quality and distribution from those in rabbits that received the cholesterol supplement alone (group I), and of different quality from but in distribution similar to those in rabbits that received horse serum alone (group II). Fatty lesions developed in small, rarely in medium, but never in large arteries of rabbits in group I, and these changes do not resemble coronary athero-arteriosclerosis in man. Proliferative lesions without fatty change developed in large, medium, and small arteries of rabbits in group II, and some of these closely resemble human coronary arteriosclerosis without fatty change. The changes that developed in large, medium, and small arteries of rabbits in group III were in very large majority fatty-proliferative lesions. Some of these closely resemble the changes that in some cases constitute coronary athero-arteriosclerosis in man. Nuclei with caterpillarlike chromatin pattern in longitudinal section and owl eye appearance in transverse section were observed to occur in many of the proliferating cells in thickened arterial intima in hearts of rabbits in groups II and III and in some of the lipid rich "foam" cells in arterial intima and subjacent media in hearts of rabbits in group III. Such nuclei have been observed to occur in some reacting smooth muscle cells and normal immature and reacting mature striated muscle cells of the heart. These observations indicate that at least many of the cells, including "foam" cells, in thickened intima in the experimentally induced and in naturally occurring coronary athero-arteriosclerosis are smooth muscle cells that evolved in proliferative reaction to arterial injury. Fatty change developed in aortas of the rabbits in groups I and III, and was significantly greater in group III. Results of this investigation support the hypothesis that the synergy of allergic injury to arteries and lipid-rich diet can lead to athero-arteriosclerosis.