Chapter 16 - Cardiovascular Disease: Mouse Models of Atherosclerosis

Abstract

Technologic advancements in the genetic modifications in mice that have occurred during the last decade have enabled the generation of multiple models that each exhibit conditions like human cardiovascular disease. Consequently, the mouse is now clearly established as the premier model for complex cardiovascular research. This chapter illustrates, with emphasis on atherosclerosis, how use of the mouse has contributed to the current knowledge of vascular disease pathogenesis. The pathology of atherosclerotic lesions developing in mice lacking apolipoprotein E or low-density lipoprotein receptor is very similar to that seen in human patients with one major limitation that the spontaneous hemorrhage and rupture associated with human plaques have not been observed reliably in mice. Genetic as well as pharmacologic approaches using the mouse models of atherosclerosis have consequently concentrated on the early stages of atherogenesis and have produced a wealth of information regarding the factors that modify the development of atherosclerosis. Surgically induced cardiac complications in the atherogenic mouse models have also been utilized to define how hyperlipidemia influences the pathogenesis of other cardiovascular diseases such as myocardial infarction and restenosis. Continued improvements can be expected in both the mouse model and the sensitivity and miniaturization of various diagnostic procedures used in their evaluation. Thus, the mouse continues to promise additional exciting and productive times in cardiovascular research.