Fibrinogen and fibrin: scaffold proteins in hemostasis.
OBJECTIVE
Elevated fibrinogen is a cardiovascular risk factor. Recent work provides a rationale for this risk, as abnormal fibrin clot structure, strength and stability correlates with coronary artery disease. This review describes in-vitro experiments whose intent is to define the molecular mechanisms that control clot architecture and function in vivo.


RESULTS
Biochemical and structural data continue to define the interactions between monomer units that assemble into a fibrin clot. In particular, 'A: a' interactions dominate the first step in fiber formation, while the analogous 'B: b' interactions have a minor role. Studies show the N-terminus of Bbeta, the C-terminus of Aalpha, and the splice variant gamma' modulate fibrin clot structure. Measurement of the mechanical properties of fibrinogen and fibrin show fibrin fibers are among the strongest in nature. Studies have identified fibrinogen-binding proteins that influence clot structure and function.


CONCLUSIONS
These findings defined mechanisms that control fibrin clot structure, strength and stability. This basic information provides direction for clinical studies to examine clot properties in pathologic thrombosis and pharmaceutical studies to develop therapeutic interventions to prevent or control cardiovascular disease. These studies also establish novel techniques to examine individual bonds, molecules and fibers.
Lord
Susan T
ST
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. stl@med.unc.edu
D001777:Blood Coagulation; D005337:Fibrin / Q000378:metabolism / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism / Q000502:physiology*; D006487:Hemostasis; D006801:Humans; D011485:Protein Binding
D005337:Fibrin; D005340:Fibrinogen