Plasma Fibronectin Concentration

Abstract

Accumulation and cohesion of platelets at sites of vascular injury are essential for the formation of the hemostatic plug but also result in thrombosis.1,2 Platelet plug or thrombus formation is initiated by interaction of platelet receptors with components of extracellular matrix (ECM) of injured vessels. Fibronectin is both an ECM component and moderately abundant 460-kDa glycoprotein in blood, present at 300 to 400 μg/mL (0.6 to 0.9 μmol/L) in plasma and 0.5 μg per 3×108 platelets in platelet α-granules.3–5 Plasma fibronectin is a dimer of nearly identical 230-kDa subunits (Figure) that can multimerize to the insoluble form found in ECM.6 Because it is a ligand of platelet surface receptors and an ECM component, fibronectin has long been suspected of playing a role in platelet biology.4,5 Interestingly, fibronectin and its type I module, of which there are 12 in fibronectin (Figure), are well characterized to date only in vertebrates.7,8 Therefore, fibronectin seems to be a recent addition to the armamentarium of proteins that function in the vertebrate vasculature. A, Diagram of dimeric plasma fibronectin. N termini are on the outsides, and C termini are in the middle. The bulk of each subunit consists of 12 type I, 2 type II, and 15 type III modules. One subunit contains the alternatively spliced V region. The N-terminal regions that bind to platelet surface sites of fibronectin assembly and RGD-containing module III-10 that binds to αIIbβ3 and other platelet integrins are indicated. Below is a simplified model in which the C-terminal region is represented as an oval and the III-10 modules as triangles. B, Depiction of interactions of fibronectin with platelets. Circulating soluble …