Active tissue factor shed from human arterial smooth muscle cells adheres to artificial surfaces

Through a series of in vitro assays, this study outlines a flow-mediated pr ocess by which active tissue factor (TF), the prime initiator of coagulatio n, may be transferred from the plasma membrane of vascular smooth muscle ce lls (VSMCs) to that of artificial surfaces such as those typically associat ed with intravascular implants. Studies with quiescent and activated rat VS MCs demonstrated that pathologically high shcar stresses (tau (w) = 250 dyn cm(-2)) resulted in the loss of TF activity from the cell surface. Subsequ ent experiments with human VSMCs showed that VSMCs continuously release act ive TF into their extracellular medium, presumably in the form of lipid ves icles or microparticles, and that fluid shear stress (tau (w) = 50 dyn cm(- 2)) or chemical agonists (A23187) can significantly accelerate this release . Experiments with a wide array of polymeric and metallic materials showed that the TF shed from VSMCs was able to adhere to these surfaces and promot e the activation of coagulation factor X (FX) at the material surface. Extr acellular TF bound strongly to both uncoated and human plasma coated surfac es under a wide range of hemodynamic shear stresses (0-20 dyn cm(-2)). When an extracellular, VSMC-derived TF mixture was perfused over Ti 6-4 surface s, the adhesion of TF was found to be time-dependent, gradually accumulatin g on the material surface over time. Thus an important criterion in the des ign or success of intravascular devices may be related to their ability to interact with TF, shed from cell surfaces. This is especially important as TF may lead to thrombotic complications, the products of which may also inc rease cellular proliferation.