ABSTRACT
Introduction Atherosclerosis bears many features of a chronic inflammation that affects the intima of the large and medium-sized arteries. Lesion formation begins with the influx from the circulation of monocytes/macrophages, which become loaded with cholesterol ester to create the fatty streak. At this stage the lesion is completely reversible. Fatty streaks may progress by the influx of additional monocytes and T cells, the products of which, along with those of endothelial cells, result in migration of smooth muscle cells (SMCs) from the media to the intima, where they proliferate and synthesize matrix components. Some cells in the plaque die, leaving a necrotic core and extra cellular cholesterol clefts, which are hallmarks of advanced lesions. The luminal face of the lesion often has a fibrous cap, generated by SMCs, which is thought to stabilize the plaque. Although the obstruction of the lumen of the vessel by the atherosclerotic plaque is a potential threat, a clinical event usually occurs as a result of a complica tion of the plaque, such as intraplaque haemorrhage causing rapid plaque expansion or rupture of the plaque surface to generate a thrombogenic surface. These late phases of the atherosclerotic plaque and of plaque rupture are receiving increasing attention from investigators. Therefore, there is increasing need for animal models that mimic end stages of atherosclerosis and plaque rupture. In this chapter I will discuss new mouse models of end-stage atherosclerosis.
