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 the arterial wall and on its surface is a consistent response to the vascular injury of angioplasty and of angioplasty lesions at risk of rapid restenosis. Mitogenic activity is stimulated by fibrin degradation products in extracts of human atherosclerotic plaques and plasmin digests of fibrin, and this has been attributed to products that include fibrin fragment E. The effect of human fibrin degradation products on smooth muscle outgrowth from rabbit aortic medial explants now has been explored in culture. Every batch of fibrin degradation products was first tested on the in vivo chick chorioallantoic membrane model for the ability to stimulate cell proliferation, including angiogenesis as shown previously. Increasing concentrations of fibrin degradation products were stimulated significantly earlier and with greater outgrowth of smooth muscle cells than controls, up to an optimum at 92 microg/mL fibrin degradation products. The effect of fibrin degradation products was blocked by the prior admixture of a specific antifragment E antiserum, but not by an antifragment D antiserum. Purified commercial fibrinogen E is inactive, but when treated with thrombin to resemble fibrin E it stimulated smooth muscle cell outgrowth, and this was not seen with comparable dosages of fragment D. We propose that fibrin degradation products, in particular fibrin fragment E, provide an abundant in situ early initiator of smooth muscle cell migration and proliferation in restenosis and atherogenesis.