Journal article
Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles
Arteriosclerosis, thrombosis, and vascular biology, Vol.26(6), pp.1391-1396
2006
DOI: 10.1161/01.ATV.0000216282.58291.c6
PMID: 16528004
Abstract
Objective: Plasma fibronectin (FN) is decreased in several clinical conditions. We were interested to study the thrombotic and hemostatic consequences of the decrease in plasma FN (pFN), the role of FN splice variants in thrombosis, and to examine whether pFN incorporates into thrombi in vivo.
Methods and results: We compared the thrombotic response to a vessel injury in FN heterozygous (FN+/-) mice and corresponding FN+/+ mice. Although normal thrombosis in venules was observed, a decrease to half in the pFN concentration in FN+/- mice caused a delay in the appearance of thrombi in arterioles and consequently a delay in their occlusion. We were able to rescue the thrombotic defect in the FN+/- mice by infusion of rat pFN. Additionally, we could show intense incorporation of fluorescent pFN-coated microspheres into the developing thrombi. Moreover, we found that mice expressing FN without the EIIIA or EIIIB domains specific to cellular FN including platelet FN had no thrombotic defect.
Conclusions: Mice heterozygous for FN have a striking defect in thrombus initiation and growth in arterioles attributable to the decrease of pFN. Our study is an example of haploid insufficiency for FN, and it emphasizes the fundamental role of this plasma protein in thrombosis in the arterial system.
Details
- Title: Subtitle
- Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles
- Creators
- Jana MATUSKOVA - CBR Institute for Biomedical Research, Harvard Medical School, Boston, United StatesAnil K CHAUHAN - CBR Institute for Biomedical Research, Harvard Medical School, Boston, United StatesBeatrice CAMBIEN - CBR Institute for Biomedical Research, Harvard Medical School, Boston, United StatesSophie ASTROF - Howard Hughes Medical Institute Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, United KingdomVandana S DOLE - CBR Institute for Biomedical Research, Harvard Medical School, Boston, United StatesCrystal L PIFFATH - CBR Institute for Biomedical Research, Harvard Medical School, Boston, United StatesRichard O HYNES - Howard Hughes Medical Institute Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, United KingdomDenisa D WAGNER - CBR Institute for Biomedical Research, Harvard Medical School, Boston, United States
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.26(6), pp.1391-1396
- Publisher
- Lippincott
- DOI
- 10.1161/01.ATV.0000216282.58291.c6
- PMID
- 16528004
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094401402771
Metrics
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