Atherosclerosis is the pathological process that underlies the development of
cardiovascular disease, a leading cause of mortality.
Atherosclerotic plaque formation is driven by the recruitment of inflammatory monocytes into the artery wall, their differentiation into macrophages and the subsequent transformation of macrophages into
cholesterol-laden foam cells. Models of hypercholesterolaemia such as the
ApoE (
apolipoprotein E)-/- mouse and the application of transgenic technologies have allowed us to undertake a thorough dissection of the cellular and molecular biology of the atherosclerotic disease process. Murine models have emphasized the central role of
inflammation in
atherogenesis and have been instrumental in the identification of adhesion molecules that support monocyte recruitment,
scavenger receptors that facilitate
cholesterol uptake by macrophages and other macrophage activation receptors. The study of mice deficient in multiple members of the
chemokine family, and their receptors, has shown that
chemokines play a critical role in promoting
atherosclerotic plaque formation. In the present review, we will discuss novel therapeutic avenues for the treatment of
cardiovascular disease that derive directly from our current understanding of
atherogenesis gained in experimental animal models.