Chapter 7. Vascular Proliferative Disease

The most common initial form of vascular proliferative disease is atherosclerosis, a vascular occlusive event that occurs over the course of many years or decades as a consequence of abnormal cholesterol deposition in vessel walls. The normal primary function of blood vessels is to carry nutrients and oxygen to vascular capillary beds and to carry metabolic products and carbon dioxide for removal from the body. Natural defense systems have evolved to insure control of these functions. These include platelet adhesion at the luminal surface of injured vessel walls that induce the formation of thrombi that lead to clot formation and prevention of bleeding into the extravascular space. In case of extensive insults to the vessel wall, inflammatory cells also accumulate to aid in vascular repair. Under certain conditions, these normal protective mechanisms are overstimulated and cause vascular diseases; the most common being atherosclerosis. The treatments for vascular proliferative diseases are numerous and diverse, including percutaneous transluminal coronary angioplasty (PTCA or balloon angioplasty), bypass or interpositional grafting, carotid endarterectomy, hemodialysis vascular access grafts, transplant, and stents. Treatments, while initially often successful, induce a secondary narrowing called restenosis. Reduction in vascular proliferative disease, such as restenosis, is a very complex challenge related to the heterogeneous expression of this disease. While sharing the common features of luminal occlusion, typically a result of the smooth muscle cells (SMC) proliferation and matrix deposition that encroach on the lumen, restenotic diseases are initiated by a wide variety of stimuli. Further, many of these stimuli occur by redundant but distinct processes.