Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan

Abstract

The NG2 proteoglycan is expressed by nascent pericytes during the early stages of angiogenesis. To investigate the functional role of NG2 in neovascularization, we have compared pathological retinal and corneal angiogenesis in wild type and NG2 null mice. During ischemic retinal neovascularization, ectopic vessels protruding into the vitreous occur twice as frequently in wild type retinas as in NG2 null retinas. In the NG2 knock-out retina, proliferation of both pericytes and endothelial cells is significantly reduced, and the pericyte:endothelial cell ratio falls to 0.24 from the wild type value of 0.86. Similarly, bFGF-induced angiogenesis is reduced more than four-fold in the NG2 null cornea compared to that seen in the wild type retina. Significantly, NG2 antibody is effective in reducing angiogenesis in the wild type cornea, suggesting that the proteoglycan can be an effective target for anti-angiogenic therapy. These experiments therefore demonstrate both the functional importance of NG2 in pericyte development and the feasibility of using pericytes as antiangiogenic targets. Keywords

Melanoma‐associated chondroitin sulphate proteoglycan as a new target antigen for CD4+ T cells in melanoma patients

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“…13 In line with these findings, NG2 knock-out mice show a significantly reduced proliferation of pericytes and endothelial cells within the retina and cornea. 13 Glioblastoma multiforme tumors transfected with NG2, showed a significantly increased neovascularization rate with a higher vascular density than control tumors in a rat model. This accelerated angiogenesis was accompanied by a dramatic increase in tumor growth.…”

Early Inhibition of MMP Activity in Ischemic Rat Brain Promotes Expression of Tight Junction Proteins and Angiogenesis During Recovery

“…In NG2 knock-out mice, proliferation of both pericytes and endothelial cells in retina in response to hypoxia is significantly reduced. 30 There are several possible mechanisms by which NG2 regulates angiogenesis; NG2 has been shown to bind directly to basic fibroblast growth factor and platelet-derived growth factor AA (PDGF-AA), and may enhance interaction of these growth factors with cell surface receptors. 16 In the present study, we showed an overexpression of NG2 in vascular-associated pericytes at 3 weeks, which is spatiotemporally expressed with MMPs, VEGF, and TJPs.…”

NG2, a novel proapoptotic receptor, opposes integrin α4 to mediate anoikis through PKCα-dependent suppression of FAK phosphorylation

“…NG2 regulates cell proliferation, migration, spreading, and adhesion in melanomas, gliomas, oligodendrocyte progenitors, and pericytes 16,17,20,21 and increases metastasis of melanoma cells. 20 It has never been implicated in apoptosis.…”