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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 20, 2007 Accepted October 16, 2007 Angiogenesis is regulated by a novel mechanism: Pro- and anti-angiogenic proteins are organized into separate platelet -granules and differentialy released Joseph E. Italiano Jr*, Jennifer L. Richardson, Sunita Patel-Hett, Elisabeth Battinelli, Alexander Zaslavsky, Sarah Short, Sandra Ryeom, Judah Folkman, and Giannoula L Klement Translational Medicine Division, Brigham and Women's Hospital, Boston, MA, United States Vascular Biology Program, Department of Surgery, Children's Hospital, Boston, MA, United States Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, MA, United States Dana-Farber Cancer Institute, Boston, MA, United States * Corresponding author; email: jitaliano{at}rics.bwh.harvard.edu. Platelets, in addition to their function in hemostasis, play an important role in wound healing and tumor growth. Because platelets contain both 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 both platelets and megakaryocytes. Double immunofluorescence labeling of VEGF (an angiogenesis stimulator) and endostatin (an angiogenesis inhibitor), or for thrombospondin-1 and basic FGF, 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 PAR-4 agonist (AYPGKF-NH2) resulted in release of endostatin-containing granules, but not VEGF-containing granules, while the selective PAR-1 agonist (TFLLR-NH2) liberated VEGF, but not endostatin-containing granules. We conclude that the separate packaging of angiogenesis regulators into pharmacologically and morphologically distinct populations of -granules in megakaryocytes and platelets may be 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: C. E. Holmes, J. C. Huang, T. R. Pace, A. B. Howard, and H. B. Muss Tamoxifen and Aromatase Inhibitors Differentially Affect Vascular Endothelial Growth Factor and Endostatin Levels in Women with Breast Cancer Clin. Cancer Res., May 15, 2008; 14(10): 3070 - 3076. [Abstract] [Full Text] [PDF] T. Goerge, B. Ho-Tin-Noe, C. Carbo, C. Benarafa, E. Remold-O'Donnell, B.-Q. Zhao, S. M. Cifuni, and D. D. Wagner Inflammation induces hemorrhage in thrombocytopenia Blood, May 15, 2008; 111(10): 4958 - 4964. [Abstract] [Full Text] [PDF] R. Flaumenhaft Platelet proteoglycans packing it in Blood, April 1, 2008; 111(7): 3308 - 3309. [Full Text] [PDF]

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