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, Inhaltsverzeichnis

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

Authors

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

Abstract

als PDF herunterladen

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.

PDF (1207 kb)

Referenzen

References
1 Gajdusek C, DiCorleto P, Ross R, Schwartz SM. An endothelial cell-derived growth factor. J Cell Biol 1980; 85: 467-472
2 Cornicelli JA, Witte LD, Goodman DS. Inhibition of LDL degradation in cultured human fibroblasts induced by endothelial cell-conditioned medium. Arteriosclerosis 1983; 3: 560-567
3 DiCorleto PE, Bowen-Pope DF. Cultured endothelial cells produce a platelet derived growth factor-like protein. USA: Proc Natl Acad Sci 1983; 80: 1919-1923
4 Witte LD, Cornicelli JA, Miller RW, Goodman DS. Effects of platelet-derived and endothelial cell-derived growth factors on the low density lipoprotein receptor pathway in cultured human fibroblasts. J Biol Chem 1982; 257: 5392-5401
5 Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature 1987; 325: 257-259
6 Sato Y, Rifkin DB. Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis. J Cell Biol 1988; 107: 1199-1205
7 Fox PL, DiCorleto PE. Regulation of production of a platelet-derived growth factor-like protein by cultured bovine aortic endothelial cells. J Cell Physiol 1984; 121: 298-308
8 Hajjar KA, Hajjar DP, Silverstein RL, Nachman RL. Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells. J Exp Med 1987; 166: 235-245
9 Gajdusek C, Carbon S, Ross R, Nawroth P, Stern D. Activation of coagulation releases endothelial cell mitogens. J Cell Biol 1986; 103: 419-428
10 Harlan JM, Thompson PJ, Ross RR, Bowen-Pope DF. α-Thrombin induces release of platelet-derived growth factor-like molecule(s) by cultured human endothelial cells. J Cell Biol 1986; 103: 1129-1133
11 Doolittle RF. Fibrinogen and fibrin. Ann Rev Biochem 1984; 53: 195-229
12 Kadish JL, Butterfield CE, Folkman J. The effect of fibrin on cultured vascular endothelial cells. Tissue Cell 1979; 11: 099-108
13 Rowland FN, Donovan MJ, Picciano PT, Wilner GD, Kreutzer DL. Fibrin-mediated vascular injury. Identification of fibrin peptides that mediate endothelial cell retraction. Am J Pathol 1984; 117: 418-428
14 Andersson RGG, Saldeen K, Saldeen T. A fibrin(ogen) derived pentapeptide induces vasodilation, prostacyclin release and an increase in cyclic AMP. Thromb Res 1983; 30: 213-218
15 Richardson DL, Pepper DS, Kay AB. Chemotaxis for human monocytes by fibrinogen-derived peptides. Br J Haematol 1976; 32: 507-513
16 Saldeen K, Christie N, Nelson WR, Movat HZ. Effect of a fibrin (ogen)-derived vasoactive peptide on polymorphonuclear leukocyte emigration. Thromb Res 1985; 37: 85-89
17 Thompson WD, Campbell R, Evans T. Fibrin degradation and angiogenesis: quantitative analysis of the angiogenic response in the chick chorioallantoic membrane. J Pathol 1985; 145: 27-37
18 Smith EB, Staples EM, Dietz HS, Smith RH. Role of endothelium in sequestration of lipoprotein and fibrinogen in aortic lesions, thrombi, and graft pseudo-intimas. Lancet 1979; ii: 812-816
19 Bini A, Fenoglio Jr JJ, Mesa-Tejada R, Kudryk B, Kaplan K. Identification and distribution of fibrinogen, fibrin, and fibrin(ogen) degradation products in atherosclerosis. Use of monoclonal antibodies. Arteriosclerosis 1989; 9: 109-121
20 Witte L, Fuks Z, Haimovitz-Friedman A, Vlodavsky I, Goodman DS, Eldor A. Effects of irradiation on the release of growth factors from cultured bovine, porcine, and human endothelial cells. Cancer Res 1989; 49: 5066-5072
21 Koehn JA, Canfield RE. Purification of human fibrinopeptides by high performance liquid chromatography. Anal Biochem 1981; 116: 349-356
22 Dreyfuss G, Adam SA, Choi YD. Physical change in cytoplasmic messenger ribonucleoproteins in cells treated with inhibitors of mRNA transcription. Mol Cell Biol 1984; 4: 415-423
23 Sobel JH, Thibodeau CA, Gawinowicz MA, Canfield RE. Immunochemical characterization of crosslinked derivatives isolated from alpha chain oligomers formed during early stages of fibrin crosslinking. Thromb Haemostas 1988; 60: 160-169
24 Rupp C, Sievi R, Furlan M. Fractionation of plasmic fibrinogen digest on lysine-agarose. Isolation of two fragments D, fragment E and simultaneous removal of plasmin. Thromb Res 1982; 27: 117-121
25 Moscatelli D. High and low affinity binding sites for basic fibroblast growth factor on cultured cells: absence of a role for low affinity binding in stimulation of plasminogen activator production by bovine capillary endothelial cells. J Cell Physiol 1987; 131: 123-130
26 Gospodarowicz D, Moran J, Braun D, Birdwell C. Clonal growth of bovine vascular endothelial cells: fibroblast growth factor as a survival agent. USA: Proc Natl Acad Sci 1976; 73: 4120-4124
27 Bowen-Pope DF, Ross R. Platelet-derived growth factor. II. Specific binding to cultured cells. J Biol Chem 1982; 257: 5161-5171
28 Ross R. The pathogenesis of atherosclerosis – An update. N Engl J Med 1986; 314: 488-500
29 Rokitansky C. A manual of pathological anatomy. London: The Sydenham Society: 1852. pp 261-273
30 Kaplan KL, Bini A. Thrombosis in atherogenesis. Crit Rev Oncol/Hematol 1989; 9: 305-318
31 Smith EB, Keen GA, Grant A, Stirk C. Fate of fibrinogen in human arterial intima. Arteriosclerosis 1990; 10: 263-275
32 Sadoshima S, Tanaka K. Fibrinogen and low density lipoprotein in the development of cerebral atherosclerosis. Atherosclerosis 1979; 34: 093-103
33 Bini A, Fenoglio Jr J, Sobel J, Owen J, Fejgl M, Kaplan KL. Immunochemical characterization of fibrinogen, Fibrin I, and Fibrin II in human thrombi and atherosclerotic lesions. Blood 1987; 69: 1038-1045
34 Watanabe K, Tanaka K. Influence of fibrin, fibrinogen and fibrinogen degradation products on cultured endothelial cells. Atherosclerosis 1983; 48: 57-70
35 Barrett TB, Benditt EP. sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery. USA: Proc Natl Acad Sci 1987; 84: 1099-1103
36 Wilcox JN, Smith KM, Williams LT, Schwartz SM, Gordon D. Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. J Clin Invest 1988; 82: 1134-1143
37 Barrett TB, Gajdusek CM, Schwartz SM, McDougall JK, Benditt EP. Expression of the sis gene by endothelial cells in culture in vivo. USA: Proc Natl Acad Sci 1984; 81: 6772-6774
38 Collins T, Ginsburg D, Boss JM, Orkin SH, Pober JS. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Nature (Lond) 1985; 316: 748-750
39 Collins T, Pober JS, Gimbrone MA, Hammacher A, Betsholtz C, Westemark B, Heldin CH. Cultured human endothelial cells express platelet-derived growth factor A chain. Am J Pathol 1987; 126: 07-12
40 Starksen NF, Harsh GR, Gibbs VC, Williams LT. Regulated expression of the platelet derived growth factor A chain gene in microvascular endothelial cells. J Biol Chem 1987; 262: 14381-14384
41 Gospodarowicz D, Neufeld G, Schweigerer L. Fibroblast growth factor. Mol Cell Endocrinol 1986; 46: 187-204
42 Vlodavsky I, Fridman R, Sullivan R, Sasse JJ, Klagsbrun M. Aortic endothelial cells synthesize, basic fibroblast growth factor which remains cell associated and platelet-derived growth factor-like protein which is secreted. J Cell Physiol 1987; 131: 402-408
43 Dejana E, Vergara-Dauden M, Balconi G, Pietra A, Cherel G, Donati MB, Larrieu MJ, Marguerie G. Specific binding of human fibrinogen to cultured human fibroblasts. Evidence for the involvement of the E domain. Eur J Biochem 1984; 139: 657-662
44 Dejana E, Languino LR, Polentarutti N, Balconi G, Ryckewaert JJ, Larrieu MJ, Donati MB, Mantovani A, Marguerie G. Interaction between fibrinogen and cultured endothelial cells. Induction of migration and specific binding. J Clin Invest 1985; 75: 11-18
45 Wang Y, Fuller GM. The putative role of fibrin fragments in the biosynthesis of fibrinogen by hepatoma cells. Biochem Biophys Res Comm 1991; 175: 562-567
46 Hatzfeld JA, Hatzfeld A, Maigne J. Fibrinogen and its fragment D stimulate proliferation of human hemopoietic cells in vitro. USA: Proc Natl Acad Sci 1982; 79: 6280-6284
47 Ishida T, Tanaka K. Effects of fibrin and fibrinogen-degradation products on the growth of rabbit aortic smooth muscle cells in culture. Atherosclerosis 1982; 44: 161-174
48 Delvos U, Muller-Berghaus G. Influence of the fibrin(ogen) degradation product fragment D on the monolayer integrity of cultured vascular endothelial cells. Failure to induce monolayer disorganization. Haemostasis 1988; 18: 099-105
49 Busch C, Gerdin B. Effect of low molecular weight fibrin degradation products on endothelial cells in culture. Thromb Res 1981; 22: 33-39
50 Gerdin B, Saldeen T. Effect of fibrin degradation products on microvascular permeability. Thromb Res 1978; 13: 0995-1006
51 McNeil PL, Muthukrishnan L, Warder E, D’Amore PA. Growth factors are released by mechanically wounded cells. J Cell Biol 1989; 109: 811-822
52 Neufeld G, Gospodarowicz D. Identification of the fibroblast growth factor receptor in human vascular endothelial cells. J Cell Physiol 1988; 136: 537-542