An investigation into the immunological theory of atherogenesis in rabbits

There is evidence to show that injections of foreign proteins in conjunction with high fat diets will produce atherosclerosis in rabbits. Furthermore, it has been suggested that patients with heart disease have higher levels of circulating milk antibodies than controls and that immunological injury might initiate the process which eventually leads to atherosclerosis. An experimental programme was designed to investigate the possibility that a regular-intake of food antigens (soya bean proteins) together with a high intake of fat might produce atherosclerosis, and an arterial disease was produced by feeding cholesterol-free, semi-synthetic diets to rabbits for eleven months. The histological features of this disease were unusual in that there was evidence of an inflammatory infiltrate with mononuclear cells and occasional giant cells. In most of the rabbits food antibodies were detected and there were significant positive correlations between plasma cholesterol levels and atherosclerosis scores and between food antibody titres and atherosclerosis scores.The above experiment was repeated to investigate more closely the immunological processes that might be involved in the development of arteriosclerosis using similar diets. The rabbits sacrificed after three months on the diets showed no arterial disease, but after nine to twelve months on the diets some disease was evident, more predominant in the nine than in the twelve month feeding trial. The arterial disease produced was less than in the first experiment and the level of food antibodies was also lower. There was a significant correlation between plasma cholesterol levels and the atherosclerosis scores and between immune complex levels and the atherosclerosis scores. A further experiment with low unsaturated fat, high starch diets was carried out. No arterial disease was produced in these rabbits, which produced food antibodies but had normal plasma cholesterol levels. Clearly, from the first experiment food antigens appear to play a role in the atherogenic process but due to the lesser extent of the disease in the second experiment this role could not be confirmed, probably because the rabbits were immunologically tolerant to the soya proteins as their mother's diet had also contained soya. The weight of evidence suggests that soluble immune complexes may be responsible for causing injury to the vessel walls. There is a need for further investigation into the effect of feeding food antigens on atherogenesis.