PR39, a peptide regulator of angiogenesis

Although tissue injury and inflammation are considered essential for the in duction of angiogenesis, the molecular controls of this cascade are mostly unknown. Here we show that a macrophage-derived peptide, PR39, inhibited th e ubiquitin-proteasome-dependent degradation of hypoxia-inducible factor-1 alpha protein, resulting in accelerated formation of vascular structures in vitro and increased myocardial vasculature in mice. For the latter, corona ry flow studies demonstrated that PR39-induced angiogenesis resulted in the production of functional blood vessels. These findings show that PR39 and related compounds can be used as potent inductors of angiogenesis, and that selective inhibition of hypoxia-inducible factor-la degradation may underl ie the mechanism of inflammation-induced angiogenesis.