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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1227-1233. Prepublished online as a Blood First Edition Paper on October 25, 2007; DOI 10.1182/blood-2007-09-113837. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-113837v1 111/3/1227    most recent Alert me when this article is cited 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Italiano, J. E. Articles by Klement, G. L. Search for Related Content PubMed PubMed Citation Articles by Italiano, J. E., Jr Articles by Klement, G. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet granules and differentially released Joseph E. Italiano, Jr1,2, Jennifer L. Richardson1, Sunita Patel-Hett1,2, Elisabeth Battinelli1,3, Alexander Zaslavsky2, Sarah Short2, Sandra Ryeom2, Judah Folkman2, and Giannoula L. Klement2,4 1 Translational Medicine Division, Brigham and Women's Hospital; 2 Vascular Biology Program, Department of Surgery, Children's Hospital; 3 Department of Hematology and Oncology, Beth Israel Deaconess Medical Center; and 4 Dana-Farber Cancer Institute, Boston, MA Platelets, in addition to their function in hemostasis, play an important role in wound healing and tumor growth. Because platelets contain angiogenesis stimulators and inhibitors, the mechanisms by which platelets regulate angiogenesis remain unclear. As platelets adhere to activated endothelium, their action can enhance or inhibit local angiogenesis. We therefore suspected a higher organization of angiogenesis regulators in platelets. Using double immunofluorescence and immunoelectron microscopy, we show that pro- and antiangiogenic proteins are separated in distinct subpopulations of -granules in platelets and megakaryocytes. Double immunofluorescence labeling of vascular endothelial growth factor (VEGF) (an angiogenesis stimulator) and endostatin (an angiogenesis inhibitor), or for thrombospondin-1 and basic fibroblast growth factor, confirms the segregation of stimulators and inhibitors into separate and distinct -granules. These observations motivated the hypothesis that distinct populations of -granules could undergo selective release. The treatment of human platelets with a selective PAR4 agonist (AYPGKF-NH2) resulted in release of endostatin-containing granules, but not VEGF-containing granules, whereas the selective PAR1 agonist (TFLLR-NH2) liberated VEGF, but not endostatin-containing granules. In conclusion, the separate packaging of angiogenesis regulators into pharmacologically and morphologically distinct populations of -granules in megakaryocytes and platelets may provide a mechanism by which platelets can locally stimulate or inhibit angiogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The yin-yang of platelet granules Charles S. Abrams Blood 2008 111: 979. [Full Text] [PDF] This article has been cited by other articles: T. I. Fortoul, A. Gonzalez-Villalva, G. Pinon-Zarate, V. Rodriguez-Lara, L. F. Montano, and L. Saldivar-Osorio Ultrastructural megakaryocyte modifications after vanadium inhalation in spleen and bone marrow J. 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