Nature Medicine
6, 49 - 55 (2000)
doi:10.1038/71527
PR39, a peptide regulator of angiogenesisJian Li1, Mark Post1, Rudiger Volk1, Youhe Gao1, Min Li1, Caroline Metais1, 3, Kaori Sato1, 3, Jo Tsai2, William Aird2, Robert D. Rosenberg4, Thomas G. Hampton1, Jianyi Li3, Frank Sellke3, Peter Carmeliet5
& Michael Simons11
Angiogenesis Research Center Beth Israel Deaconess
Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA
2
Division of Hematology and Molecular Medicine Beth
Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA
3
Department of Medicine, Department of Surgery both
at Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA
4
Department of Biology, MIT, Cambridge, Massachusetts 02139, USA
5
Catholic University of Leuven, Leuven, Belgium
Correspondence should be addressed to Michael Simons msimons@caregroup.harvard.eduAlthough 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-1
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-1 degradation may underlie the mechanism
of inflammation-induced angiogenesis.
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