Alterations of Fibrinogen Structure in Human Disease

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Abstract:

Products of normal and pathologic metabolism can react with proteins to cause covalent modification. When such modifications affect fibrinogen they can potentially alter fibrinogen function. Those that have been best studied are oxidation, nitration, homocysteinylation and glycation. It appears that the clottability of fibrinogen is maintained unless the degree of modification is extensive. However, modest degrees of fibrinogen modification can alter the rate of assembly of fibrin monomers into a fibrin clot and the fiber structure and packing. In addition, some types of modification affect lysine residues that are critical to binding, activation and activity of fibrinolytic enzymes. Any of these alterations could potentially affect the susceptibility of fibrin clots to fibrinolysis, and have been shown to do so in vitro. In the case of homocysteinylation and glycation, good evidence exists that fibrinogen modification affects clot stability in vivo. However, direct evidence is still lacking that these modifications contribute to the increased atherothrombotic risk associated with hyperhomocysteinemia and diabetes.

Keywords: Oxidation; nitration; homocysteinylation; glycation; fibrinolysis

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152508784871981

Publication date: 2008-07-01

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  • Cardiovascular & Hematological Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Cardiovascular & Hematological Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Cardiovascular & Hematological medicinal chemistry.

    Cardiovascular & Hematological Agents in Medicinal Chemistry
    is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cardiovascular & hematological drug discovery.
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