In humans, atherosclerotic plaques develop within pre-existing diffuse intimal thickenings. The vast majority of cells in these intimal thickenings are smooth muscle, and it is their nodular proliferation, synthesis of extracellular matrix and accumulation of intra- and extracellular lipid which results in the development of the lesion. Two of the crucial initiating or progression events in atherogenesis are the invasion of monocyte/macrophages into the vessel wall as a result of hyperlipidemia, and endothelial denudation or dysfunction with resultant platelet aggregation and release. Products from these cells interact with smooth muscle, modifying its phenotype and influencing its behaviour and response.