PR39, a peptide regulator of angiogenesis

  • An Erratum to this article was published on 01 March 2000

Abstract

Although tissue injury and inflammation are considered essential for the induction of angiogenesis, the molecular controls of this cascade are mostly unknown. Here we show that a macrophage-derived peptide, PR39, inhibited the ubiquitin–proteasome-dependent degradation of hypoxia-inducible factor-1α protein, resulting in accelerated formation of vascular structures in vitro and increased myocardial vasculature in mice. For the latter, coronary 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-1α degradation may underlie the mechanism of inflammation-induced angiogenesis.

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Figure 1: Matrigel assays.
Figure 2: PR39 induces HIF-1αand HIF-1α-dependent gene expression.
Figure 3: Angiogenesis in αMHC–PR39 mice.
Figure 4: PR39 induction of angiogenesis in lacZ transgenic mice.
Figure 5: Physiologic evaluation of PR39-induced angiogenesis
Figure 6: Effect of PR39 administration in the setting of acute myocardial ischemia.

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Acknowledgements

This work was supported in part by National Institutes of Health grants R01 HL53793 and P50 HL 56993 (M.S.), HL 46716 (F.W.S.), F32 HL10013 (R.V.), American Heart Association Established Investigator Award (M.S.) and by a grant from Chiron Corporation (M.S.).

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Correspondence to Michael Simons.

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Li, J., Post, M., Volk, R. et al. PR39, a peptide regulator of angiogenesis. Nat Med 6, 49–55 (2000). https://doi.org/10.1038/71527

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