RESTENOSIS FOLLOWING CORONARY ANGIOPLASTY - CLINICAL, CELLBIOLOGICAL AND MOLECULAR ASPECTS

Percutaneous transluminal coronary angioplasty by balloon dilatation ( PTCA) has proved to be the standard procedure for non-operative remova l of coronary artery stenoses. Since the initial description and appli cation by Andreas Gruntzig, the results of this procedure are excellen t with an acute success rate of 90-96 %, a rate of severe acute compli cations of 1 % and less, and a procedure-related death rate below 1 %, mainly due to considerable technical improvements and greater experie nce of the interventional cardiologists. On the other hand, the resten osis rate following PTCA could not be significantly lowered. In recent years a number of alternative angioplasty devices has been developed aimed at - among other indications - reducing the restenosis rate foll owing PTCA by a ''less traumatic'' vessel angioplasty. These include r adiofrequency angioplasty (RFCA), high frequency rotational angioplast y (HFRCA), excimer-laser angioplasty (ELCA), directional atherectomy ( DCA), as well as implantation of intravascular stents. Based on more o r less extensive experiences from the literature, the aim at lowering the recurrency rate by the latter procedures has been missed, despite the fact that particularly ELCA and HFRCA were used to reduce stenoses in lesions unsuitable for balloon catheter dilatation. There is a tre nd of lowering the recurrence rate with the implantation of coronary s tents. The benefit of this procedure, however, is at the expense of an increased rate of acute stent thrombosis and by local acute bleeding problems quite often requiring surgical repair. The cellular biologica l mechanisms following balloon angioplasty are only partially understo od. Among these are a number of interactive processes like cell adhesi on, coagulation, vascular contraction, cell migration, cell proliferat ion, and synthesis of extracellular matrix. In this respect, migration and proliferation of smooth muscle cells represent a key process for the development of restenosis. In addition, endothelial denudation rep resents a stimulus for migration and proliferation of smooth muscle ce lls. Rapid and efficient reendothelialization may counteract this proc ess. Recent progress of modern biology has provided new concepts and m ethodological tools for the molecular analysis of vascular remodeling. It has been shown that specialized cellular functions such as prolife ration, migration, and production of extracellular matrix can be media ted by growth factors such as platelet-derived growth factor (PDGF), b asic fibroblast growth factor (bFGF) or transforming growth factor-bet a (TGF-beta). Moreover, involvement of these factors in complex proces ses of angioplasty-induced vascular remodeling has been demonstrated. The modulation of growth factors or growth factor-dependent signaling represents a new therapeutic concept for molecular interventions. Diff erent approaches including gene therapy could be applied to inhibit pr oliferation of smooth muscle cells or to stimulate reendothelializatio n of arterial segments following angioplasty. However, such developmen ts are still in an experimental and preclinical stage, and they are no t yet available for clinical testing.