Heart Care Info - Heart Disease Prevention & Treatment

The role of an experimental model of atherosclerosis: apoE-knockout mice in developing new drugs against atherogenesis.

J Jawien - Current pharmaceutical biotechnology, 2012 - Although atherosclerosis was previously thought to be mainly a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. There was a pivotal role of apo E-knockout mice in understanding the inflammatory background of atherosclerosis. ...

Although atherosclerosis was previously thought to be mainly a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. There was a pivotal role of apo E-knockout mice in understanding the inflammatory background of atherosclerosis. Currently, atherosclerosis is known as a chronic inflammatory disease, in most cases initiated by hypercholesterolemia. Since 1992 the mouse has become an excellent model for experimental atherosclerosis research. Until 1992, the diet-induced atherosclerosis mouse model has been used effectively, but the lesions tended to be small and were limited to early fatty-streak stage. This model was also criticized because of the toxicity and inflammatory responses due to the diet. In 1992 the first line of gene targeted animal models, namely apolipoprotein E-knockout mice was developed. Of the genetically engineered models, the apo E-deficient model is the only one that develops extensive atherosclerotic lesions on a chow diet. It is also the model in which the lesions have been characterized most thoroughly. The lesions develop into fibrous plaques; however, there is no evidence that plaque rupture occurs in this model. The LDL receptor - deficient model has elevated LDL levels, but no lesions, or only very small lesions, form on the chow diet, however, robust lesions do form on the western-type diet. The creation of apo E-knockout mice has changed the face of atherosclerosis research. The apo E-deficient mouse model of atherosclerosis can then be used to: 1) identify atherosclerosis susceptibility modifying genes, by the candidate-gene and gene-mapping methods; 2) identify the role of various cell types in atherogenesis; 3) identify environmental factors affecting atherogenesis; and 4) assess therapies that might block atherogenesis or lesion progression. Apo E-deficient mice have also been used to look for environmental and drug effects on atherosclerosis and to test novel therapies. Gene-targeted mouse models has changed the face of atherosclerotic research and helped in creation of the new theory of atherosclerosis - as an inflammatory disease. Nowadays, apo E-knockout mice model is therefore used in developing new drugs against atherosclerosis. This review describes how new groups of agents are searched.