Tissue Factor–Bearing Microparticles and Thrombus Formation

Abstract—Blood microparticles are vesicular structures with a diameter of 100 to 1000 nm that are present in the blood of normal subjects and in patients with various diseases. These microparticles are derived from cells that circulate in the blood and cells associated with the blood vessel wall. Microparticle membranes retain the protein receptors of their parent cells and may retain RNAs and other cytosolic content. On the basis of surface protein expression, microparticles are known to be derived from platelets, granulocytes, monocytes, endothelial cells, smooth muscle cells, and tumor cells. Only a subpopulation of these microparticles expresses tissue factor. (Arterioscler Thromb Vasc Biol. 2011;31:728-733.) Key Words: arterial thrombosis blood coagulation endothelium microcirculation platelets thrombosis microparticles Tissue factor is an integral membrane protein that ispresent on the plasma membrane of many cells not exposed to blood. This protein, a receptor for factor VII and factor VIIa, is required for the initiation of blood coagulation. Tissue factor, composed of 263 amino acid residues,1,2 includes an N-terminal extracellular domain of 219 amino acids, a transmembrane domain of 23 amino acids, and a 21-residue C-terminal cytoplasmic domain containing palmi-tate and stearate bound to a cysteine.3 The extracellular domain is homologous to other members of the cytokine receptor superfamily. Tissue factor binds factor VIIa to form the tissue factor/factor VIIa complex on the cell surface that activates factor IX, factor X, and factor VII.4 The x-ray structure of tissue factor5 and the complex of the active site-inhibited factor VIIa and extracellular domain of tissue factor have been determined,6 and others have further refined this structure.7 This article accompanies the ATVB in Focus: Microparticles series that was published in th