Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles.
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.


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.
Matuskova
Jana
J
CBR Institute for Biomedical Research, Harvard Medical School, Boston, USA.
Chauhan
Anil K
AK
Cambien
Beatrice
B
Astrof
Sophie
S
Dole
Vandana S
VS
Piffath
Crystal L
CL
Hynes
Richard O
RO
Wagner
Denisa D
DD
D017398:Alternative Splicing; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control; D001160:Arterioles / Q000187:drug effects*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism; D002712:Chlorides; D005290:Ferric Compounds / Q000494:pharmacology; D005353:Fibronectins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D006238:Haploidy; D006579:Heterozygote; D051379:Mice; D018345:Mice, Knockout; D010973:Platelet Adhesiveness / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D013152:Splanchnic Circulation; D013927:Thrombosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D014699:Venules
D002712:Chlorides; D005290:Ferric Compounds; D005353:Fibronectins; C024555:ferric chloride