Abstract
Beta 2 glycoprotein I (beta 2GPI) is the major auto antigen in the antiphospholipid syndrome but also interacts with fibrinolytic and angiogenic proteins. The aim of this study was to examine the angiogenic potential of beta 2GPI in vivo in beta 2GPI deficient mice utilizing angiogenic assays. beta 2GPI deficient mice show increased microvessel formation in comparison to beta 2GPI replete controls when injected with growth factor free-matrigel implants. However, microvessel formation in matrigel plugs of beta 2GPI deficient mice was less than in beta 2GPI replete mice when basic fibroblast growth factor (bFGF) was included in the matrigel. Hemoglobin content was higher in vascular endothelial growth factor (VEGF) containing-matrigel plugs in the beta 2GPI deficient mouse demonstrating that the lack of beta 2GPI led to increased extravasation by VEGF. Melanoma B16F10 tumour growth was enhanced in beta 2GPI deficient mice. Melanoma microvessel density was increased in beta 2GPI deficient mice but the proliferation rate of tumour cells (determined by Ki67 immunohistochemistry) was unaffected by the presence or absence of beta 2GPI. Subcutaneous delivery of native human beta 2GPI by the ALZET osmotic pump did not affect melanoma tumour growth in beta 2GPI deficient mice. We conclude that the in vivo unopposed action of beta 2GPI is anti-angiogenic however this function is modified in the presence of a strong angiogenic stimulus into stabilization of vessel formation. Although the presence of beta 2GPI attenuates vessel sprouting in certain tumours, no survival benefit is conferred to tumour bearing animals. This does not preclude the potential benefit of modified or fragments of beta 2GPI in anti-angiogenesis research. (C) 2010 Elsevier Ltd. All rights reserved.