CXCL4 Integrins Angiogenesis 45. Ashton AW, Cheng Y, Helisch A, Ware JA (2004) Thromboxane A2 receptor agonists antagonize the proangiogenic effects of fibroblast growth factor-2: role of receptor internalization, thrombospondin-1, and avb3. Circ Res 94: 735–42. 46. Perollet C, Han ZC, Savona C, Caen JP, Bikfalvi A (1998) Platelet factor-4 modulates fibroblast growth factor-2 activity and inhibits FGF-2 dimerization. Blood 91: 3289–99. 47. Gengrinovitch S, Greenberg SM, Cohen T, Gitay-Goren H, Rockwell P, et al. (1995) Platelet factor-4 inhibits the mitogenic activity of VEGF121 and VEGF165 using several concurrent mechanisms. J Biol Chem 270: 15059–65. 48. Sato Y, Abe M, Takaki R (1990) Platelet factor-4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells. Biochem Biophys Res Commun 172: 595–600. 49. Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, et al. (2003) An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 197: 1537–49. 50. Sulpice E, Contreres JO, Lacour J, Bryckaert M, Tobelem G (2004) Platelet factor 4 disrupts the intracellular signalling cascade induced by vascular endothelial growth factor by both KDR dependent and independent mechanisms. Eur J Biochem 271: 3310–8. 51. Gentilini G, Kirschbaum NE, Augustine JA, Aster RH, Visentin GP (1999) Inhibition of human umbilical vein endothelial cell proliferation by the CXC chemokine, platelet factor 4 (CXCL4), is associated with impaired downregu- lation of p21(Cip1/WAF1). Blood 93: 25–33. 52. Wickstro¨m SA, Alitalo K, Keski-Oja J (2004) An endostatin-derived peptide interacts with integrins and regulates actin cytoskeleton and migration of endothelial cells. J Biol Chem. 279: 20178–85. 53. Shiraga M, Richie A, Aidoudi S, Baron V, Wilcox D, et al. (1999) Primary megakaryoctes reveal a role for transcription factor NF-E2 in integrin aIIbb3 signaling. J Cell Biol 147: 1419–1429. 54. Gao J, Zoller KE, Ginsberg MH, Brugge JS, Shattil SJ (1997) Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3. EMBO J 16: 6414–25. PLoS ONE | www.plosone.org 14 July 2008 | Volume 3 | Issue 7 | e2657