期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 2, 页码 856-861出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911661107
关键词
angiogenesis; antiangiogenic therapy; neovascularization; mural cells; vascular permeability
资金
- Swedish Research Council
- Swedish Cancer Foundation
- Karolinska Institute Foundation
- Swedish Synframjandets Research Foundation
- Karolinska Gender Foundation
- Torsten and Ragnar Soderberg's Foundation
- European Union [504743]
- VascuPlug [STRP 013811]
VEGF coordinates complex regulation of cellular regeneration and interactions between endothelial and perivascular cells; dysfunction of the VEGF signaling system leads to retinopathy. Here, we show that systemic delivery of VEGF and placental growth factor (PlGF) by protein implantation, tumors, and adenoviral vectors ablates pericytes from the mature retinal vasculature through the VEGF receptor 1 (VEGFR1)-mediated signaling pathway, leading to increased vascular leakage. In contrast, we demonstrate VEGF receptor 2 (VEGFR2) is primarily expressed in nonvascular photo-receptors and ganglion cells. Moreover, blockade of VEGFR1 but not VEGFR2 significantly restores pericyte saturation in mature retinal vessels. Our findings link VEGF and PlGF to cancer-associated retinopathy, reveal the molecular mechanisms of VEGFR1 ligand-mediated retinopathy, and define VEGFR1 as an important target of antiangiogenic therapy for treatment of retinopathy.
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