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Fibrin monomer and fibrinopeptide B act additively to increase DNA synthesis in smooth muscle cells cultured from human saphenous vein

Sturge, Justin; Carey, Nessa; Davies, Alun H.; Powell, Janet T.

Authors

Nessa Carey

Alun H. Davies

Janet T. Powell



Abstract

Purpose: We investigated the hypothesis that fibrinogen increased DNA synthesis (and cell proliferation) of smooth muscle cells (SMCs) cultured from human saphenous vein and that the increased DNA synthesis was attenuated when cells were cultured on polymeric collagen. Methods: SMCs were cultured from human saphenous vein on plastic, fibronectin, monomeric, and polymeric collagen. Fibrinogen products were prepared by proteolytic digestion. DNA synthesis was measured by bromodeoxyuridine incorporation into DNA, cell proliferation by cell counting, cyclic adenosine monophosphate by enzyme-linked immunosorbent assay, and fibrinopeptide B labeled with iodine 125 used for binding studies. Results: Fibrin monomer (0.003-0.1 μmol/L) stimulated a concentration-dependent increase in DNA synthesis of up to 10-fold, which could be inhibited by the peptide Bβ15-42. The stimulation of DNA synthesis was highest for cells cultured on plastic and lowest for cells cultured on type I collagen polymer. Much higher concentrations of fibrinogen (0.3-1 μmol/L) were required to effect similar increases in DNA synthesis. Fibrinogen had a particular effect to augment DNA synthesis, up to 14-fold, when cells were cultured on monomeric type I collagen. This augmented DNA synthesis was inhibited by a neutralizing antibody to urokinase-type plasminogen activator. Incubation of cells cultured on collagen monomer with fibrinogen resulted in production of fibrinopeptide B. Fibrinopeptide B (5 μmol/L) increased DNA synthesis by fourfold and had additive effects with fibrin monomer to increase DNA synthesis. Iodinated tyrosine fibrinopeptide B bound to SMCs (dissociation constant 0.6 μmol/L). Conclusion: Cultured human saphenous vein SMCs appear to have high-affinity receptors for fibrin monomer and fibrinopeptide B, the engagement of which stimulates DNA synthesis. These mechanisms may be pertinent to the association between fibrinogen and vein graft stenosis in vivo. (J Vasc Surg 2001;33:847-53.)

Journal Article Type Article
Publication Date 2001-04
Journal Journal of Vascular Surgery
Print ISSN 0741-5214
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 33
Issue 4
Pages 847-853
Institution Citation Sturge, J., Carey, N., Davies, A. H., & Powell, J. T. (2001). Fibrin monomer and fibrinopeptide B act additively to increase DNA synthesis in smooth muscle cells cultured from human saphenous vein. Journal of vascular surgery, 33(4), 847-853. https://doi.org/10.1067/mva.2001.111984
DOI https://doi.org/10.1067/mva.2001.111984
Keywords Surgery; Cardiology and Cardiovascular Medicine
Publisher URL https://www.sciencedirect.com/science/article/pii/S0741521401788064?via%3Dihub