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

J. J. Hathcock, C. L. Hall, V. T. Turitto

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Through a series of in vitro assays, this study outlines a flow-mediated process by which active tissue factor (TF), the prime initiator of coagulation, may be transferred from the plasma membrane of vascular smooth muscle cells (VSMCs) to that of artificial surfaces such as those typically associated with intravascular implants. Studies with quiescent and activated rat VSMCs demonstrated that pathologically high shear stresses (τW = 250 dyn cm-2) resulted in the loss of TF activity from the cell surface. Subsequent experiments with human VSMCs showed that VSMCs continuously release active TF into their extracellular medium, presumably in the form of lipid vesicles or microparticles, and that fluid shear stress (τW = 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 promote the activation of coagulation factor X (FX) at the material surface. Extracellular TF bound strongly to both uncoated and human plasma coated surfaces 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 surfaces, the adhesion of TF was found to be time-dependent, gradually accumulating on the material surface over time. Thus an important criterion in the design 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 increase cellular proliferation.

Original languageEnglish
Pages (from-to)1211-1225
Number of pages15
JournalJournal of Biomaterials Science, Polymer Edition
Volume11
Issue number11
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Artificial surfaces
  • Microparticles
  • Thrombosis
  • Tissue factor
  • Vascular smooth muscle

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