Atherosclerosis is a complex, multifactorial disease with both genetic and
environmental determinants. Experimental investigation of the effects of th
ese determinants on the development and progression of atherosclerosis has
been greatly facilitated by the use of targeted mouse models of the disease
, particularly those resulting from the absence of functional genes for apo
lipoprotein E or the low density lipoprotein receptor (LDLR). This review f
ocuses on the influence on atherosclerosis of combining apoE or LDLR defici
encies with factors affecting atherogenesis, including (1) inflammatory pro
cesses, (2) glucose metabolism, (3) blood pressure, and (4) coagulation and
fibrinolysis. We also discuss the general problem of using the mouse to te
st the effects on atherogenesis of human polymorphic variations and future
ways of enhancing the usefulness of these mouse models.