Timecourse of fibrin deposition and removal after arterial injury

Abstract

Atherosclerosis is a major disease of our aging society. It models of atherosclerosis and in-stent neointimal formation is commonly treated by angioplasty, in which a balloon is inflated in the artery to dilate the vessel and crush the primary lesion, or by stenting, in which a metallic brace is placed in the vessel after angioplasty. These treatments may result in immediate occlusive complications (1–8% of patients) or restenosis, a subsequent reblocking of the artery within 6 months of surgery (up to 60% of cases) [1–3]. Restenosis is due to a number of processes: intimal hyperplasia, vessel remodelling and/or thrombus deposition. Animal models of stenosis have shown that both vascular remodelling and neointimal hyperplasia determine the final luminal area [4,5]. Additionally, luminal narrowing may result from inclusion and absorption of agents of the thrombotic state (platelets, fibrin and erythrocytes) [6–8]. Thrombus and the presence of fibrin may play an active role in many other instances of restenosis. While normal aorta contains little fibrin or fibrinogen, early atherosclerotic plaques contain fibrin(ogen) present as long threads surrounding macrophages and other cells in the artery wall [9]. Although thrombi are not associated with uncomplicated plaques, insoluble fibrin and fibrinogen are concentrated in the shoulder region and necrotic core of the plaque [10,11]. Fibrin(ogen) has chemotactic and mitogenic effects and may act as a scaffold for smooth muscle cell migration and cell recruitment, adding to the size of the plaque [12,13]. Angioplasty results in localised areas of arterial wall damage, including endothelial denudation and, in extreme cases, medial stretching and splitting [1,2]. When the endothelium is removed, there is a loss of thrombosis inhibition normally present, platelets are deposited and adhesive molecules exposed [6,14]. There are several animal