Cardiovascular Research 2004 63(2):226-235; doi:10.1016/j.cardiores.2004.04.012
© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Differential role of platelet granular mediators in angiogenesis
Blood Coagulation Unit, Hematology Department, Hadassah Medical Center, Jerusalem, Israel
* Corresponding author. Tel.: +972-2-6776756; fax: +972-2-6449580. Email address: brilla{at}hadassah.org.il
Objectives: Platelets contain numerous substances regulating angiogenic response. However, the regulatory role of platelets in blood vessel development remains to be elucidated. We investigated the comprehensive effect of platelets as a cellular system on angiogenesis. Methods: The following approaches were applied: (a) in vitro-aortic ring assay and chemotaxis assay; (b) in vivo-injection of platelet-containing matrigel plug subcutaneously into a mouse followed by immunohistochemical analysis of angiogenic response. Results: Platelets stimulated formation of blood vessels in vitro in the rat aortic ring model via VEGF and bFGF, while blocking of platelet factor-4 promoted this effect. Addition of platelets to the matrigel followed by its subcutaneous injection into a mouse resulted in an intensive migration of fibroblasts into the matrigel as well as formation of blood capillaries de novo. This platelet effect was mediated through bFGF, VEGF, and heparanase. Furthermore, platelet releasate was found to induce endothelial cell chemotaxis. This effect was mediated by a concerted action of intraplatelet bFGF, PDGF, VEGF, and heparanase. Conclusion: Platelets affect different stages of the angiogenic response with a trend to a pro-angiogenic net effect despite the presence of angiogenesis inhibitors such as platelet factor 4. While a concomitant effect of bFGF and VEGF seemed to be essential for the entire process of vessel formation (aortic ring and matrigel models), PDGF and heparanase were effective only at the migration stage.
KEYWORDS Platelets; Angiogenesis
1 These authors have contributed equally to this study.
Time for primary review 20 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Feng, N. P. McCabe, G. H. Mahabeleshwar, P. R. Somanath, D. R. Phillips, and T. V. Byzova The angiogenic response is dictated by {beta}3 integrin on bone marrow-derived cells J. Cell Biol., December 15, 2008; 183(6): 1145 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yang, B. R. Mwaikambo, T. Zhu, C. Gagnon, J. Lafleur, S. Seshadri, P. Lachapelle, J.-C. Lavoie, S. Chemtob, and P. Hardy Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R467 - R476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M.W. Verheul, M. P.J. Lolkema, D. Z. Qian, Y. H.A. Hilkes, E. Liapi, J.-W. N. Akkerman, R. Pili, and E. E. Voest Platelets Take Up the Monoclonal Antibody Bevacizumab Clin. Cancer Res., September 15, 2007; 13(18): 5341 - 5347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kisucka, C. E. Butterfield, D. G. Duda, S. C. Eichenberger, S. Saffaripour, J. Ware, Z. M. Ruggeri, R. K. Jain, J. Folkman, and D. D. Wagner Platelets and platelet adhesion support angiogenesis while preventing excessive hemorrhage PNAS, January 24, 2006; 103(4): 855 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Iversen and H. Wiig Tumor Necrosis Factor {alpha} and Adiponectin in Bone Marrow Interstitial Fluid from Patients with Acute Myeloid Leukemia Inhibit Normal Hematopoiesis Clin. Cancer Res., October 1, 2005; 11(19): 6793 - 6799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Boulanger and A. Tedgui Dying for attention: Microparticles and angiogenesis Cardiovasc Res, July 1, 2005; 67(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
|
|
A. Brill, O. Dashevsky, J. Rivo, Y. Gozal, and D. Varon Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization Cardiovasc Res, July 1, 2005; 67(1): 30 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Krotz, H.-Y. Sohn, and U. Pohl Reactive Oxygen Species: Players in the Platelet Game Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1988 - 1996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D Blann Angiogenesis and platelets: the clot thickens further Cardiovasc Res, August 1, 2004; 63(2): 192 - 193. [Full Text] [PDF]
|
|