Atherosclerosis: Activation of the injured vessel wall

Effective prevention and management of atherosclerosis requires an understanding of the sequence of events leading to the initiation and growth of the fibrofatty plaque. An area of intense investigation into understanding the pathogenesis of atherosclerosis is the cell biology of the vessel wall. Since the advent of tissue culture methods to study pure populations of large vessel endothelial and smooth muscle cells, the role of these vascular wall cells in the development and the subsequent growth of the fibrofatty plaque has been extensively investigated to give new insight into human atherogenesis. The major contribution of cell biology has been to show that the vascular endothelial cells are very active metabolically and are able to interact with other important physiologic processes that occur at the blood-vascular wall interface, including coagulation fibrinolysis, platelet aggregation, leukocyte adherence, and migration. Smooth muscle cells have been shown to be very active metabolically, synthesizing the matrix components of the atherosclerotic plaque. It has also been shown that endothelial cells have the potential to modulate smooth muscle cell function within the vessel wall and vice versa by the release of locally acting polypeptides and glycoproteins and by direct intercellular communications. The studies to be reviewed in this chapter support two concepts. The first is that the endothelial and smooth muscle cells maintain the physiologic homeostasis of the vessel wall. The second is that new stable states are achieved by these cells when normal homeostasis is lost following injury. In these new stable states, the vessel continues to function as a conduit for blood flow but is more likely to form the pathobiologic fibrofatty plaque.