Low Molecular Weight Fibrinogen Degradation Products Stimulate the Release of Growth Factors from Endothelial Cells

Roberto Lorenzet; Joan H Sobel; Alessandra Bini; Larry D Witte

doi:10.1055/s-0038-1656380

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 68(03): 357-363
DOI: 10.1055/s-0038-1656380

Original Article

Schattauer GmbH Stuttgart

Low Molecular Weight Fibrinogen Degradation Products Stimulate the Release of Growth Factors from Endothelial Cells

Roberto Lorenzet

¹The Istituto di Ricerche Farmacologiche “Mario Negri”, Consorzio Mario Negri Sud, S. Maria Imbaro (CH), Italy

,

Joan H Sobel

²The Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA

,

Alessandra Bini

¹The Istituto di Ricerche Farmacologiche “Mario Negri”, Consorzio Mario Negri Sud, S. Maria Imbaro (CH), Italy

³The Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

,

Larry D Witte

²The Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA

› Author Affiliations

Abstract

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Summary

Cultured porcine aortic endothelial cells (PAEC) constitutively produce and secrete in their culture medium mitogens collectively called endothelial cell-derived growth factors (EDGFs). Incubation of PAEC with fibrinogen-degradation products (FDPs) obtained by plasmin digestion of highly purified fibrinogen caused an increased release of EDGFs, as assessed by [³H]-thymidine incorporation in 3T3 mouse fibroblasts. The effect was time-dependent and correlated with the degree of fibrinogenolysis. It was accompanied by elongation of the cells. Neither increase in EDGFs release nor cell damage was observed when non-degraded fibrinogen was incubated with endothelial cells. Low molecular weight fibrinogen degradation products (LMWFDPs) (M _r ≤ 10,000), and the higher molecular weight fibrinogen fragments D and E were tested under the same conditions. Only the LMWFDPs caused elongation and damage to PAEC and a marked stimulation (up to 12 fold) of EDGFs release. A low density growth assay revealed that the released EDGFs were mitogenically active on the same PAEC. The activity of the released EDGFs was time and dose dependent on both 3T3 fibroblasts and PAEC, indicating that LMWFDPs caused enhanced release of EDGFs that can act in paracrine and autocrine fashion. This study suggests an additional role for fibrinogenolysis contributing to wound healing, and possibly to atherosclerosis.

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References

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