Effects of Thrombin on Interactions between β3-Integrins and Extracellular Matrix in Platelets and Vascular Cells

George A. Stouffer, S. S. Smyth

Research output: Contribution to journalShort surveypeer-review

43 Scopus citations

Abstract

The β3-integrin family consists of α IIbβ3 (also known as glycoprotein IIb/IIIa) and αvβ3. αIIbβ3 is found on platelets and megakaryocytes and has an essential role in hemostasis. αvβ3 has a broader distribution, and it functions in angiogenesis, neointimal formation after vascular injury, and leukocyte trafficking. There are important interactions between thrombin and β3-integrins relative to both "inside-out" (integrin activation) and "outside-in" (modification of cellular events by ligand binding to integrins) signaling. Thrombin, by binding to G protein-coupled, protease-activated receptors, is a potent activator of αIIbβ3. Conversely, outside-in signaling through αIIbβ3 amplifies events initiated by thrombin and is necessary for full platelet spreading, platelet aggregation, granule secretion, and the formation of a stable platelet thrombus. In smooth muscle cells, αvβ3-integrins influence various responses to thrombin, including proliferation, c-Jun NH2-terminal kinase-1 activation, and focal adhesion formation. Other interactions between β3-integrins and thrombin include β3-integrin promotion of the generation of thrombin by localizing prothrombin to cellular surfaces and/or enhancing the formation of procoagulant microparticles and the requirement of β3-integrin function for platelet-dependent clot retraction. In summary, there is increasing evidence that interactions between β3-integrins and thrombin play important roles in the regulation of hemostatic and vascular functions.

Original languageEnglish
Pages (from-to)1971-1978
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number11
DOIs
StatePublished - Nov 2003

Keywords

  • Cell adhesion molecules
  • Muscle, smooth
  • Platelets
  • Signal transduction
  • Thrombin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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