ABSTRACT
The arterial wall, far from being a simple conduit for the passive transport of blood, is a metabolically highly active and complex structure composed of cellular units interdependent upon and affecting each other in a large array of homeostatic and reparative processes. The arterial wall is constantly subjected to injurious stimuli, both mechanical stimuli in the form of shear forces, intravascular pressure, and wall tension, as well as chemical stimuli including certain lipoproteins and a host of metabolic waste products bathing the endothelial surface. The maintenance of vascular integrity is dependent upon both a remarkable resistance to injury and upon a complex set of reparative pathways which in turn are largely dependent upon a variety of cell-cell interactions mediated by biochemical messengers. These messages are transmitted largely in a paracrine system, but both endocrine and autocrine modalities may also play a role. The interplay between endothelial cell and smooth muscle cell migration and proliferation and the regulation of these events by messages from these cell types, from adherent platelets, and from adherent leukocytes and infiltrating monocytes/macrophages determines whether the response to injurious stimuli will be restorative or pathologic. A central feature of the developing atherosclerotic lesion is the overabundant proliferation of the smooth muscle cell and the production by it of extracellular matrix components. Similar events occur following other injuries including the implantation of vascular prostheses with resultant pseudointimal hyperplasia, and following certain experimentally induced injuries including large scale endothelial denudation. Proliferating smooth muscle cells undergo phenotypic alteration resulting in increased synthetic activity as well as modulation of lipoprotein metabolic pathways. The regulation of smooth muscle proliferation in response to injury is highly complex and involves both stimulatory and inhibitory messages. These messages, in the form of growth factors, are now being elucidated. The stimuli regulating the production and release of these growth factors and the mechanisms by which they transfer their message to the target cells remain poorly understood and are central to our understanding and eventual control of atherogenesis.
