Building better vasculature

  • Bruick R
  • McKnight S
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Abstract

Throughout embryogenesis, establishment of the vascu- lar network is mediated by a complex and highly regu- lated interplay between positive and negative growth factors. In adults, this vascular network is relatively stable and formation of new microvasculature is gener- ally associated with pathophysiological conditions such as tumorigenesis, ischemic insult, and chronic inflam- matory diseases. Vascular endothelial growth factor (VEGF) is a critical positive regulator of both physiologi- cal and pathophysiological neovascularization. As such, VEGF has become an important therapeutic target in the fight against cancer, blindness resulting from age-related macular degeneration or diabetic retinopathy, and pul- monary hypertension. Conversely, induction of VEGF with the intent to promote angiogenesis may benefit pa- tients suffering from myocardial ischemia, limb isch- emia resulting from diabetes, and insufficient wound healing. While overexpression of VEGF alone has been shown to promote angiogenesis, the resulting capillaries are often leaky and accompanied by edema, inflamma- tion, and spontaneous hemorrhagic ulcers. In contrast, the article authored by Elson and colleagues in this issue (Elson et al. 2001) demonstrates that induction of VEGF expression in basal keratinocytes by a constitutively ac- tive, gene-specific transcription factor results in in- creased dermal vascularization devoid of leakage or in- flammation. These findings suggest important new therapeutic avenues for promoting angiogenesis and pro- vide a context in which to assess the relative contribu- tions of VEGF to the formation of new vasculature.

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Authors

  • R. K. Bruick

  • S. L. McKnight

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