Journal article
Prothrombotic effects of fibronectin isoforms containing the EDA domain
Arteriosclerosis, thrombosis, and vascular biology, Vol.28(2), pp.296-301
02/2008
DOI: 10.1161/ATVBAHA.107.149146
PMID: 17991876
Abstract
Fibronectin (FN) plays an important role in the formation of stable arterial thrombi at the site of vascular injury. FN containing Extra Domain A (EDA+ FN) is absent from normal plasma, but elevated plasma levels of EDA+ FN are found in several pathological conditions. We hypothesized that EDA+ FN plays a special role in thrombosis.
We used mouse strains constitutively including (EDA+/+) or excluding (EDA-/-) the EDA domain in all tissues and plasma. Using a flow chamber and the ferric-chloride injury model we found that EDA+ FN accelerates thrombosis both in vitro and in vivo at arterial shear rates. In EDA+/+ mice thrombi (>30 microm) grew faster when compared with EDA(WT/WT) (6.6+/-0.2 minutes versus 8.3+/-0.6 minutes, P<0.05) and the mean vessel occlusion time was shorter (9.9+/-0.4 minutes versus 14.6+/-1.7 minutes, P<0.05). However, the presence of EDA+ FN affected neither single platelet adhesion to subendothelium nor thrombosis in veins. In addition, the mortality rate of EDA+/+ mice after collagen/epinephrine infusion was twice that of EDA(WT/WT) or EDA-/- mice.
Our findings reveal that EDA+ FN has prothrombotic activity, and its presence in plasma may worsen pathological conditions in which this form is elevated.
Details
- Title: Subtitle
- Prothrombotic effects of fibronectin isoforms containing the EDA domain
- Creators
- Anil K Chauhan - Harvard Medical SchoolJanka Kisucka - Harvard UniversityMaria R Cozzi - Centro di Riferimento OncologicoMeghan T Walsh - Harvard UniversityFederico A Moretti - International Centre for Genetic Engineering and BiotechnologyMonica Battiston - Centro di Riferimento OncologicoMario Mazzucato - Centro di Riferimento OncologicoLuigi De Marco - Centro di Riferimento OncologicoFrancisco E Baralle - International Centre for Genetic Engineering and BiotechnologyDenisa D Wagner - Harvard UniversityAndrés F Muro - International Centre for Genetic Engineering and Biotechnology
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.28(2), pp.296-301
- DOI
- 10.1161/ATVBAHA.107.149146
- PMID
- 17991876
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Grant note
- R37 HL41002 / NHLBI NIH HHS GGP06147 / Telethon R37 HL041002 / NHLBI NIH HHS
- Language
- English
- Date published
- 02/2008
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359677002771
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