title: Cause-effect relation between hyperfibrinogenemia and vascular disease.
abstract: Elevated plasma levels of fibrinogen are associated with the presence of cardiovascular disease, but it is controversial whether elevated fibrinogen causally imparts an increased risk, and as such is a true modifier of cardiovascular disease, or is merely associated with disease. By investigating a transgenic mouse model of hyperfibrinogenemia, we show that elevated plasma fibrinogen concentration (1) elicits augmented fibrin deposition in specific organs, (2) interacts with an independent modifier of hemostatic activity to regulate fibrin turnover/deposition, (3) exacerbates neointimal hyperplasia in an experimental model of stasis-induced vascular remodeling, yet (4) may suppress thrombin generation in response to a procoagulant challenge. These findings provide direct experimental evidence that hyperfibrinogenemia is more than a by-product of cardiovascular disease and may function independently or interactively to modulate the severity and/or progression of vascular disease.
authors: Blood Research Institute, Blood Center of SE Wisconsin, Milwaukee 53226, USA.
authors: Bryce
authors: B
authors: Kerlin
authors: Brian C
authors: BC
authors: Cooley
authors: Berend H
authors: BH
authors: Isermann
authors: Irene
authors: I
authors: Hernandez
authors: Rashmi
authors: R
authors: Sood
authors: Mark
authors: M
authors: Zogg
authors: Sara B
authors: SB
authors: Hendrickson
authors: Michael W
authors: MW
authors: Mosesson
authors: Susan
authors: S
authors: Lord
authors: Hartmut
authors: H
authors: Weiler
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D002712:Chlorides; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019281:Dimerization; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005290:Ferric Compounds / Q000494:pharmacology; D005340:Fibrinogen / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology*
chemical_list: D002712:Chlorides; D003432:Cross-Linking Reagents; D005290:Ferric Compounds; D005340:Fibrinogen; D013917:Thrombin; C024555:ferric chloride