This Article Full Text Full Text (PDF) All Versions of this Article: 23/11/1971    most recent 01.ATV.0000093470.51580.0Fv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stouffer, G.A. Articles by Smyth, S.S. Search for Related Content PubMed PubMed Citation Articles by Stouffer, G.A. Articles by Smyth, S.S. Related Collections Cell signalling/signal transduction Smooth muscle proliferation and differentiation Thrombin Extracellular Mediators in Atherosclerosis and Thrombosis Platelets

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1971.)
© 2003 American Heart Association, Inc.

Brief Reviews

Effects of Thrombin on Interactions Between ß₃-Integrins and Extracellular Matrix in Platelets and Vascular Cells

G.A. Stouffer; S.S. Smyth

From the Division of Cardiology and Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill.

Correspondence to George A. Stouffer, MD, Division of Cardiology, University of North Carolina, Chapel Hill, NC 27599-7075. E-mail rstouff{at}med.unc.edu

Series Editor: Marschall S. Runge
ATVB In Focus

Extracellular Mediators in Atherosclerosis and Thrombosis

Previous Brief Review in this Series:

•Brasier AR, Recinos A III, Eledrisi MS. Vascular inflammation and the renin-angiotensin system. 2002;22:1257–1266.
•Moser M. Patterson C. Thrombin and vascular development: a sticky subject. 2003;23:922–930.
•Major CD, Santulli RJ, Derian CK, Andrade-Gordon P. Extracellular mediators in atherosclerosis and thombosis: lessons from thrombin receptor knockout mice. 2003;23:931–939.
•Yin Y-J, Salah Z, Grisaru-Granovsky S, Cohen I, Even-Ram SC, Maoz M, Uziely B, Peretz T, Bar-Shavit R. Human protese-activated receptor 1 expression in malignant epithelia: a role in invasiveness. 2003;23:940–944.

The ß₃-integrin family consists of _IIbß₃ (also known as glycoprotein IIb/IIIa) and _vß₃. _IIbß₃ is found on platelets and megakaryocytes and has an essential role in hemostasis. _vß₃ has a broader distribution, and it functions in angiogenesis, neointimal formation after vascular injury, and leukocyte trafficking. There are important interactions between thrombin and ß₃-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 _IIbß₃. Conversely, outside-in signaling through _IIbß₃ 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, _vß₃-integrins influence various responses to thrombin, including proliferation, c-Jun NH₂-terminal kinase-1 activation, and focal adhesion formation. Other interactions between ß₃-integrins and thrombin include ß₃-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 ß₃-integrin function for platelet-dependent clot retraction. In summary, there is increasing evidence that interactions between ß₃-integrins and thrombin play important roles in the regulation of hemostatic and vascular functions.

Key Words: thrombin • platelets • cell adhesion molecules • muscle, smooth • signal transduction

This article has been cited by other articles:

				P. Zania, M. Papaconstantinou, C. S. Flordellis, M. E. Maragoudakis, and N. E. Tsopanoglou Thrombin mediates mitogenesis and survival of human endothelial cells through distinct mechanisms Am J Physiol Cell Physiol, May 1, 2008; 294(5): C1215 - C1226. [Abstract] [Full Text] [PDF]

				M. Valiyaveettil, N. Kar, M. Z. Ashraf, T. V. Byzova, M. Febbraio, and E. A. Podrez Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI Blood, February 15, 2008; 111(4): 1962 - 1971. [Abstract] [Full Text] [PDF]

				A. M. Lechner, I. Assfalg-Machleidt, S. Zahler, M. Stoeckelhuber, W. Machleidt, M. Jochum, and D. K. Nagler RGD-dependent Binding of Procathepsin X to Integrin {alpha}vbeta3 Mediates Cell-adhesive Properties J. Biol. Chem., December 22, 2006; 281(51): 39588 - 39597. [Abstract] [Full Text] [PDF]

				S. Rieken, S. Herroeder, A. Sassmann, B. Wallenwein, A. Moers, S. Offermanns, and N. Wettschureck Lysophospholipids Control Integrin-dependent Adhesion in Splenic B Cells through Gi and G12/G13 Family G-proteins but Not through Gq/G11 J. Biol. Chem., December 1, 2006; 281(48): 36985 - 36992. [Abstract] [Full Text] [PDF]

				M. E. Papaconstantinou, C. J. Carrell, A. O. Pineda, K. M. Bobofchak, F. S. Mathews, C. S. Flordellis, M. E. Maragoudakis, N. E. Tsopanoglou, and E. Di Cera Thrombin Functions through Its RGD Sequence in a Non-canonical Conformation J. Biol. Chem., August 19, 2005; 280(33): 29393 - 29396. [Abstract] [Full Text] [PDF]