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Fibrinogen: structure, function, and surface interactions.

Abstract

Fibrinogen plays a central role in the mechanism of coagulation and thrombosis and is partially involved in the development of postintervention restenosis. Because of therapeutic implications, it is convenient for the vascular interventionalist to revisit its structure, function, and relationships within the vascular environment. This review focuses on the molecular structure, mechanisms of polymerization and lysis, and fibrinogen interaction with the platelet alpha(IIb)beta(3) [corrected] integrin. It also addresses the less understood interaction of fibrinogen with artificial surfaces. Glycoprotein IIb-IIIa blockers, targeted to interfere with fibrinogen-platelet interactions, widely used in clinical practice, are discussed, and trials of new drugs are also summarized.

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BibTeXRIS

C Fuss, J C Palmaz, E A Sprague. 2001. Fibrinogen: structure, function, and surface interactions.. https://doi.org/10.1016/s1051-0443(07)61437-7

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Mutation of W215 compromises thrombin cleavage of fibrinogen, but not of PAR1 or protein C.

W215 is a highly conserved residue that shapes the S3 and S4 specificity sites of thrombin. Replacement of W215 with Phe produces modest effects on thrombin function, whereas the W215Y replacement significantly compromises the amidolytic activity toward synthetic and natural substrates. Replacement of W215 with Ala reduces fibrinogen and PAR4 cleavage 500-fold and 280-fold, respectively. On the other hand, the mutant decreases protein C activation and PAR1 cleavage only threefold and 25-fold, respectively. The W215A mutant cleaves PAR1 with a specificity constant more than 13-fold greater than that of fibrinogen and protein C, and 800-fold greater than PAR4. This is the first thrombin derivative to be described that functions as an almost exclusive activator of PAR1. The environment of W215 influences differentially three physiologically important interactions of thrombin, a feature that should assist in the separate study of each of these functions in vivo.

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