EXPERIMENTAL MODELS OF THE ATHEROSCLEROSIS ON RABBITS

Abstract

Atherosclerosis is the main cause of cardiovascular diseases, which, despite a number of new advances in their diagnosis and treatment, still occupy a leading position. Experimental modeling of atherosclerosis in laboratory animals plays an important role in the study of the fundamental pathophysiological processes and pathology of atherosclerosis. Rabbits are among the most suitable animals for simulating atherosclerosis, as they are widely available, inexpensive to maintain, and easy to manipulate. The key advantage of rabbits over other animals is that their lipid metabolism is practically similar to that of humans. The aim of the study was to analyze literature data on experimental models of atherosclerosis in rabbits. The review shows that the history of the study of atherosclerosis by means of experimental models is very rich and originates from the works of the well-known Russian pathologists A.I. Ignatovsky, N.N. Anichkov, S.S. Khalatov (1908-1915), who developed a cholesterol model of the formation of atherosclerosis in rabbits. The principle of this model is to feed laboratory animals with food containing elevated levels of lipids and cholesterol. The composition of the cholesterol (atherogenic) diet may vary, determining the existence of modifications of this model. Most often, a diet with a cholesterol content of 0.3-0.5% is used, in cases where it is necessary to accelerate the development of atherosclerosis, a short-term use of a diet with a 1% cholesterol content is allowed. In addition to cholesterol, it is recommended to use vegetable oils (soybean, coconut or corn) in the atherogenic diet as they improve the absorption of cholesterol in the intestine. In 1980, Japanese researcher Y. Watanabe deduced a new model of atherosclerosis formation - on hereditarily determined hyperlipidemic rabbits Watanabe (WHHL-rabbits). WHHL rabbits contain a genetic mutation in the gene encoding low-density lipoprotein receptors, which results in these animals having high plasma cholesterol levels with a normal diet. Thanks to modern genetic technologies, various genetic models of atherosclerosis in rabbits have also been created: transgenic and “knocked out” rabbits. The main method for obtaining transgenic rabbits is pronuclear microinjection, which allows the introduction of a transgene (additional DNA fragment) into their genome. To date, using this technology, it has been possible to introduce more than a dozen genes responsible for lipid metabolism. The principle of creating knocked out rabbits consists in specific inactivation using genome editing technologies (ZFN, TALEN, CRISPR / Cas9) of a certain working gene. Experimental models of atherosclerosis in rabbits have not lost their significance and continue to be used to study the fundamental morphological (pathological) and pathological mechanisms underlying atherosclerosis, to search for new diagnostic biomarkers and potential targets for therapeutic effects, as well as to conduct preclinical trials of newly developed drugs.