Mouse models of atherosclerosis

Atherosclerosis is a complex disease in which progressive cellular changes occur for decades before the acute manifestation of cardiovascular disease. Definition of atherogenic mechanisms in humans is hindered by the complexity and chronicity of the disease process, combined with the inability to sequentially characterize lesions in an individual patient because of shortcomings in noninvasive detection modalities. Therefore, there has been a reliance on animal models of the disease to define mechanistic pathways. Over the last decade, the mouse has become the predominant species used to create models of atherosclerosis. The initial interest was based on the great diversity of inbred strains with defined genetic backgrounds that provides a means of linking genes to the development of atherosclerosis. More recently, the ability to genetically modify mice to over or under express specific genes has facilitated the definition of pathways in the atherogenic process. All of the current mouse models of atherosclerosis are based on perturbations of lipoprotein metabolism through dietary and/or genetic manipulations. Although hyperlipidemia is necessary for the development of atherosclerosis, mouse models have demonstrated that many nonlipid factors can influence the severity and characteristics of lesions. This review selectively highlights some of the most commonly used mouse models of atherosclerosis and compare their lesions to those formed in the human disease.