Nikolaj Nikolajewitsch Anitschkow (1885-1964) established the cholesterol-fed rabbit as a model for atherosclerosis research

The cholesterol-fed rabbit is a widely used model for experimental atherosclerosis research. In regard to this, one name is periodically mentioned: Nikolaj Nikolajewitsch Anitschkow. Those infrequent reminders of an important name in modern medical history do not pay an adequate tribute to basic findings concerning the pathology and pathogenesis of atherosclerosis. In contrast to research groups at that time conducting experiments with protein enriched diets, Anitschkow demonstrated, in 1913 in St. Petersburg, that it was cholesterol only that caused these atherosclerotic changes in the rabbit arterial intima, which was very similar to human atherosclerosis. By analysing the plaque's development and histology, Anitschkow was able to identify the cell types, on which modern atherosclerosis research is now focussing with a new set of immunohistochemical methods: smooth muscle cells, macrophages and lymphocytes. He noted early (fatty streaks) and advanced (atheromatous plaques) lesions and, by standardizing cholesterol feeding, he discovered that the amount of cholesterol uptake was directly proportional to the degree of atherosclerosis formation. His explanation for this observation was what modern terminology calls 'response-to-injury'. With modern immunohistochemical and molecular-biological methods, the cholesterol-fed rabbit can be used to investigate the pathophysiological aspects which also contribute to human atherosclerosis, such as lipoproteins, diabetes, mitogens, growth-factors, adhesion molecules, endothelial-function, receptor-pathways or platelets. This model can be combined with a number of other methods causing endothelial dysfunction and injury, such as balloon denudation, electric stimulation, cuff implantation, artificial hypertension, diabetes or infection. Bred strains of hereditary hypercholesterolemic rabbits or those resistant to a cholesterol-diet provide further possibilities to expand experimental designs.