Linked Life Data

11159525

Source:http://linkedlifedata.com/resource/pubmed/id/11159525

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-2-22
pubmed:abstractText
A congenital dysfibrinogenemia, fibrinogen(Nieuwegein), was discovered in a young man without any thromboembolic complications or bleeding. A homozygous insertion of a single nucleotide (C) in codon Aalpha 453 (Pro) introduced a stop codon at position 454, which resulted in the deletion of the carboxyl-terminal segment Aalpha 454-610. The ensuing unpaired cysteine at Aalpha 442 generated fibrinogen-albumin complexes of different molecular weights. The molecular abnormalities of fibrinogen(Nieuwegein) led to a delayed clotting and a fibrin network with a low turbidity. Electron microscopy confirmed that thin fibrin bundles were organized in a fine network. The use of fibrinogen(Nieuwegein)-derived fibrin (fibrin(Nieuwegein)) in an in vitro angiogenesis model resulted in a strong reduction of tube formation. The ingrowth of human microvascular endothelial cells (hMVEC) was independent of alpha(v)beta(3), indicating that the reduced ingrowth is not due to the absence of the RGD-adhesion site at position Aalpha 572-574. Rather, the altered structure of fibrin(Nieuwegein) is the cause, since partial normalization of the fibrin network by lowering the pH during polymerization resulted in an increased tube formation. Whereas factor XIIIa further decreased the ingrowth of hMVEC in fibrin(Nieuwegein), tissue transglutaminase (TG), which is released in areas of vessel injury, did not. This is in line with the absence of the cross-linking site for TG in the alpha-chains of fibrinogen(Nieuwegein). In conclusion, this newly discovered congenital dysfibrinogenemia has a delayed clotting time and leads to the formation of an altered fibrin structure, which could not be cross-linked by TG and which is less supportive for ingrowth of endothelial cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
973-80
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:11159525-Adult, pubmed-meshheading:11159525-Afibrinogenemia, pubmed-meshheading:11159525-Biopolymers, pubmed-meshheading:11159525-Capillaries, pubmed-meshheading:11159525-Cells, Cultured, pubmed-meshheading:11159525-Codon, Terminator, pubmed-meshheading:11159525-Endothelium, Vascular, pubmed-meshheading:11159525-Exons, pubmed-meshheading:11159525-Fibrin, pubmed-meshheading:11159525-Fibrinogens, Abnormal, pubmed-meshheading:11159525-Humans, pubmed-meshheading:11159525-Male, pubmed-meshheading:11159525-Microscopy, Electron, pubmed-meshheading:11159525-Molecular Weight, pubmed-meshheading:11159525-Mutagenesis, Insertional, pubmed-meshheading:11159525-Neovascularization, Physiologic, pubmed-meshheading:11159525-Oligopeptides, pubmed-meshheading:11159525-Partial Thromboplastin Time, pubmed-meshheading:11159525-Receptors, Vitronectin, pubmed-meshheading:11159525-Sequence Deletion, pubmed-meshheading:11159525-Structure-Activity Relationship, pubmed-meshheading:11159525-Transglutaminases
pubmed:year
2001
pubmed:articleTitle
Aberrant fibrin formation and cross-linking of fibrinogen Nieuwegein, a variant with a shortened Aalpha-chain, alters endothelial capillary tube formation.
pubmed:affiliation
Gaubius Laboratory, TNO-PG, Leiden, The Netherlands.
pubmed:publicationType
Journal Article, Case Reports