Fibrin forms the cohesive network of hemostatic plugs and thrombi, and
it also provides the temporary matrix for initial support of healing
and revascularization. Because cell proliferation is needed for revasc
ularization after vessel injury, we have characterized structural requ
irements of fibrin needed to support cell proliferation on fibrin in v
itro, Proliferation of cultured human endothelial cells and fibroblast
s was measured by H-3-thymidine incorporation on fibrin surfaces varyi
ng in structure. Fibrin prepared with thrombin and lacking both fibrin
opeptides A and B (desAB fibrin) supported proliferation of both endot
helial cells and fibroblasts. In contrast, fibrin prepared with reptil
ase, which cleaves only fibrinopeptide A, supported significantly less
proliferation. Also, fibrin prepared by thrombin treatment of fibrino
gen lacking residues beta 1-42 supported only a low level of prolifera
tion. Therefore, fibrinopeptide B cleavage and exposure of beta 15-42
enhanced proliferation of cells on fibrin. Specific proteolytic inhibi
tors were used to eliminate the potential mitogenic effects of residua
l fibrin bound thrombin. Additional controls showed that neither catal
ytically inactive thrombin nor addition of the thrombin receptor-activ
ating peptide (SFLLRNPNDKYEPF [SFLL]) stimulated proliferation on desA
fibrin. The results indicate that cell proliferation on fibrin is enh
anced by fibrinopeptide B cleavage and exposure of the amino terminus
of the fibrin beta chain. They also show that specific structural feat
ures of the temporary fibrin matrix formed at sites of injury may modu
late the proliferative response of vascular cells. (C) 1995 by The Ame
rican Society of Hematology.