INFLUENCE OF ANGIOPLASTY ON MATRIX SIGNALLING AND METABOLISM

Our concepts of the pathophysiology of restenosis have undergone several changes in the last few years. Restenosis has traditionally been attributed to the growth of a neointimal lesion, known as intimai hyperplasia (Figure 1). Smooth muscle cell (SMC) proliferation and migration were central to this concept of restenosis. This prompted research strategies to prevent restenosis by targeting (unsuccessfully) SMC proliferation. These early concepts of restenosis have been altered by the awareness of the significance of various extracellular matrix (ECM) protein accumulation (including collagen, elastin and proteoglycans) in contributing to and modulating neointimal hyperplasia. In addition, a second process, termed “vascular remodelling”, which involves a contracture of the outer vessel circumference, is now appreciated as a second important process leading to restenosis. Recent observations have also suggested that the relative contribution of these 2 processes (intimai hyperplasia and vascular remodeling) to restenosis may be quite different, depending on the type of coronary intervention. While the mechanisms responsible for intimal hyperplasia and “vascular remodeling” remain poorly understood, the extracellular matrix appears to be an integral part of the vascular response to injury in the intima and probably in the adventitia as well. Thus, the perspective in this book chapter is on the role of matrix proteins in the restenotic process.