ABSTRACT
Restenosis remains the most frequent and recalcitrant problem encountered with percutaneous and surgical vascular intervention in the treatment of peripheral arterial disease (PAD). The cellular response to balloon injury of the vascular endothelium is characterized by a brisk proliferative response of smooth muscle cells (SMCs) and the deposition of extracellular matrix at the injury site, resulting in the formation of a neointima that eventually compromises luminal integrity. Although Glagovian remodeling1 allows for some compensatory enlargement at restenotic parameters of up to 40% diameter stenosis (first noted in human coronary arteries), this adaptive mechanism is lost at higher degrees of luminal narrowing. Abnormal endothelial function at the site of injury also contributes to the process by compromising the vessel’s ability to adaptively remodel. Endothelial damage and platelet activation cause the stimulation of the proliferative response by means of the mitogenic signal transducers plateletderived growth factor (PDGF), basic fibroblastic growth factor (bFGF), and angiotensin II. Fuster’s classification of the restenotic model has been extensively studied in both animals and humans. The immediate response to balloon injury occurs within the first 24 hours and is characterized by vessel recoil. Within 2 weeks of injury, there is the formation of mural thrombus at the injury site with connective tissue proliferation and organ-
ization. The activation of SMCs and the synthesis of extracellular matrix then ensue and may persist for up to 3 months post injury. In vessel segments covered early by regenerating endothelium, the proliferation of intimal SMCs is arrested prior to those in regions which remain denuded of endothelium.2,3
The clinical expression of this process is well documented in humans undergoing revascularization for PAD. Myointimal hyperplasia is a problem encountered in carotid endarterectomy (CEA) and infrainguinal surgical bypass grafting, leading to late operative failure with graft thrombosis, and in percutaneous transluminal angioplasty (PTA) with its attendant high restenosis rates. Post operative flow-limiting lesions tend to manifest within the first 6 months following surgery and are variably associated with symptoms, to the differing extents to which blood flow in the vessel becomes impeded.
