Smooth muscle cell outgrowth stimulated by fibrin degradation products: The potential role of fibrin fragment E in restenosis and atherogenesis

This study is based on the observation that deposition of thrombus within t he arterial wall and on its surface is a consistent response to the vascula r injury of angioplasty and of angioplasty lesions at risk of rapid resteno sis. Mitogenic activity is stimulated by fibrin degradation products in ext racts of human atherosclerotic plaques and plasmin digests of fibrin, and t his has been attributed to products that include fibrin fragment E. The eff ect of human fibrin degradation products on smooth muscle outgrowth from ra bbit aortic medial explants now has been explored in culture. Every batch o f fibrin degradation products was first tested on the in vivo chick chorioa llantoic membrane model for the ability to stimulate cell proliferation, in cluding angiogenesis as shown previously. Increasing concentrations of fibr in degradation products were stimulated significantly earlier and with grea ter outgrowth of smooth muscle cells than controls, up to an optimum at 92 mu g/mL fibrin degradation products. The effect of fibrin degradation produ cts was blocked by the prior admixture of a specific antifragment E antiser um, but not by an antifragment D antiserum. Purified commercial fibrinogen E is inactive, but when treated with thrombin to resemble fibrin E it stimu lated smooth muscle cell outgrowth, and this was not seen with comparable d osages of fragment D, We propose that fibrin degradation products, in parti cular fibrin fragment E, provide an abundant in situ early initiator of smo oth muscle cell migration and proliferation in restenosis and atherogenesis . (C) 2000 Elsevier Science Ltd. All rights reserved.