On the Identification of Beneficial and Detrimental Molecular Forms of Fibrinogen

Henschen-Edman, Agnes H.

doi:10.1159/000022498

Cited by 15 publications

(16 citation statements)

References 13 publications

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“…23,24 Alphastatin is derived from the human fibrinogen ␣-chain sequence, therefore it was necessary to establish that human alphastatin inhibited murine endothelial cell function prior to the evaluation of activity in vivo. Alphastatin was found to inhibit tubule formation by the murine microvascular endothelial cell line, SVEC4-10, both in the absence and presence of the growth factors bFGF and VEGF (data not shown).…”

Section: Effects Of Alphastatin On Murine Cells In Vitromentioning

confidence: 99%

Alphastatin, a 24–amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo

Staton

Brown

Rodgers

et al. 2004

Blood

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Section: Effects Of Alphastatin On Murine Cells In Vitromentioning

confidence: 99%

Alphastatin, a 24–amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo

Staton

Brown

Rodgers

et al. 2004

Blood

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“…The amino termini of these chains are joined together in a central domain that can be isolated as a single fragment from a plasmin digestion of fibrinogen (13). During blood coagulation, fibrinogen participates in both the cellular phase and the fluid phase of blood clot formation (14,15). Fibrinogen can be converted into an insoluble fibrin clot as a consequence of thrombin-catalyzed removal of fibrinopeptides A (FpA, A␣-(20 -35)) 2 and B (FpB, B␤-(31-44)) from the A␣ and B␤ chains (16).…”

mentioning

confidence: 99%

Matrix Metalloproteinases Collagenase-2, Macrophage Elastase, Collagenase-3, and Membrane Type 1-Matrix Metalloproteinase Impair Clotting by Degradation of Fibrinogen and Factor XII

Hiller

Lichte

Oberpichler

et al. 2000

Journal of Biological Chemistry

121

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The effects of plasma proteins on controlling the activity of matrix metalloproteinases (MMPs, matrixins) have been the focus of numerous studies, although only a few have examined the influence of matrixins on plasma proteins. Recently, it has been shown that MMPs may play a role in the degradation of fibrin. We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system. Our data demonstrate that the catalytic domains of MMP-8, MMP-12, MMP-13, and MMP-14 can proteolytically process fibrinogen and, with the exception of MMP-8, also inactivate Factor XII (Hageman factor). We have identified the amino termini of the major protein fragments. Cleavage of fibrinogen occurred in all chains and resulted in significantly impaired clotting. Moreover, rapid proteolytic inactivation of Factor XII (Hageman factor) by MMP-12, MMP-13, and MMP-14 was noted. These results support the hypothesis of an impaired thrombolytic potential of MMP-degraded Factor XII in vivo. MMPinduced degradation of fibrinogen supports a plasminindependent fibrinolysis mechanism. Consequently, degradation of these proteins may be important in inflammation, atherosclerosis, and angiogenesis, all of which are known to be influenced by MMP activity.The matrix metalloproteinases, MMPs 1 and matrixins, form a family of structurally and functionally related zinc-containing endopeptidases. Together they are able to degrade most of the constituents of the extracellular matrix such as basement membrane, collagens, proteoglycans, fibronectin, and laminin (1). Thus, they are implicated in connective tissue remodeling processes associated with embryonic development, pregnancy, growth, and wound repair (2). The deleterious potential of the MMPs is normally controlled by the endogenous and specific tissue inhibitors of metalloproteinases or the more general nonspecific ␣ 2 -macroglobulin (3). Disturbance of the well balanced equilibrium of MMPs and tissue inhibitors of metalloproteinases results in pathological situations such as rheumatoid and osteoarthritis, atherosclerosis, tumor growth, metastasis, and fibrosis (4-8). In addition to degradation of extracellular matrix constituents, plasma proteins such as serpins (9) or fibrinogen and cross-linked fibrin (10-12) are also cleaved.Fibrinogen is a 340-kDa dimeric glycoprotein consisting of a pair of three polypeptide chains A␣, B␤, and ␥ that are interconnected by 29 disulfide bonds. The amino termini of these chains are joined together in a central domain that can be isolated as a single fragment from a plasmin digestion of fibrinogen (13). During blood coagulation, fibrinogen participates in both the cellular phase and the fluid phase of blood clot formation (14, 15). Fibrinogen can be converted into an insoluble fibrin clot as a consequence of thrombin-catalyzed removal of fibrinopeptides A (FpA, A␣-(20 -35)) 2 and B (FpB...

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“…The addition of either a Bβ or Aα chain gives rise to a [AαBβγ] halfmolecule, which dimerizes to form the functional hexamer (10). The protein undergoes several post-translational modifications in the Golgi complex, including maturation of N-linked oligosaccharides, phosphorylation, hydroxylation and sulfation (11).…”

Section: Fibrinogen Biosynthesismentioning

confidence: 99%

Molecular Basis of Fibrinogen Deficiency

Neerman-Arbez¹

2006

Pathophysiol Haemos Thromb

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On the Identification of Beneficial and Detrimental Molecular Forms of Fibrinogen

Cited by 15 publications

References 13 publications

Alphastatin, a 24–amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo

Alphastatin, a 24–amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo

Matrix Metalloproteinases Collagenase-2, Macrophage Elastase, Collagenase-3, and Membrane Type 1-Matrix Metalloproteinase Impair Clotting by Degradation of Fibrinogen and Factor XII

Molecular Basis of Fibrinogen Deficiency

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