Emerging roles of fibronectin in thrombosis

Abstract

Fibronectin (FN) is a glycoprotein recognized originally in the 1940's as a contaminant of fibrinogen in Cohn fraction I of plasma. Decades of research demonstrated FN synthesis by a variety of cells and defined FN as an essential component of the extracellular matrix with roles in embryogenesis, development, and wound healing. More recently, FN has emerged as player in platelet thrombus formation and diseases associated with thrombosis including vascular remodeling, atherosclerosis, and cardiac repair following a myocardial infarct. We discuss the mechanisms by which this might occur and conclude that FN may have a unique role in thrombosis without affecting normal hemostasis and therefore may be a reasonable therapeutic target for the prevention of thrombotic diseases.

Figure 1. Drawing of platelet thrombus volume versus concentration in the in vitro flow assay

This drawing depicts the relationship between platelet thrombus volume after 5 min of flow of a mixture of platelets, red cells, and FN over a surface coated with FN-fibrin and the concentration of FN used in coating and during the perfusion(29). Arrows labeled (+/+), (+/-), and (-/-) approximate the plasma FN concentration in C57BL/6J mice with two alleles (+/+) of plasma FN, heterozygotes with a knock-out of plasma FN (+/-), and homozygotes for the conditional knock-out of plasma FN (-/-), respectively(38-40). Also located are approximations of the mean values of FN concentration of diseased (solid arrows) and non-diseased subjects (broken arrows) in surveys of plasma FN concentration of patients with coronary disease conducted in China (C)(35), Turkey (T1)(31); (T2)(32); (T3)(34), Korea (K)(33), and United States (US)(36).