Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 4, Pages 855-860Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0510412103
Keywords
thrombocytopenic mice; blood vessel; alpha-granule; cornea; collagen receptor
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Funding
- NCI NIH HHS [R01 CA064481, P01 CA080124, CA064481, CA80124] Funding Source: Medline
- NHLBI NIH HHS [R01 HL050545, P01 HL056949, HL31950, R37 HL041002, P01 HL031950, HL50545, R01 HL042846, HL41102, R01 HL050545-14, HL56949, HL42846, R01 HL041002, R37 HL042846] Funding Source: Medline
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Platelets contain both pro- and antiangiogenic factors, but their regulatory role in angiogenesis is poorly understood. Although previous studies showed that platelets stimulate angiogenesis in vitro, the role of platelets in angiogenesis in vivo is largely uncharacterized. To address this topic, we used two in vivo approaches, the cornea micropocket assay and the Matrigel model, in four animal models: thrombocytopenic, Lyst(bg) (platelet storage pool deficiency), glycoprotein (GP) Ib alpha/IL4R transgenic (lacking extracellular GPIb alpha, the receptor for von Willebrand factor as well as other adhesive and procoagulant proteins), and Fc gamma R-/- (lacking functional GPVI, the collagen receptor) mice. Adult mice were rendered thrombocytopenic by i.p. administration of an antiplatelet antibody. The number of growing vessels in the thrombocytopenic mice was lower in the cornea assay, and they showed significantly increased appearance of hemorrhage compared with mice treated with control IgG. The thrombocytopenic mice also showed more protein leakage and developed hematomas in the Matrigel model. GPIlb alpha/IL4R transgenic mice presented increased hemorrhage in both assays, but it was less severe than in the platelet-depleted mice. Fc gamma R-/- and LyStbg mice showed no defect in experimental angiogenesis. Intravital microscopy revealed a > 3-fold increase in platelet adhesion to angiogenic vessels of Matrigel compared with mature quiescent skin vessels. Our results suggest that the presence of platelets not only stimulates angiogenic vessel growth but also plays a critical role in preventing hemorrhage from the angiogenic vessels. The adhesion function of platelets, as mediated by GPIba, significantly contributes to the process.
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